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Cellular and Molecular Signatures of Androgen Ablation of Prostate Cancer

  • Clifford G. Tepper
  • Hsing-Jien Kung
Chapter

Abstract

Androgen ablative therapy is the cornerstone of treatment for metastatic prostate cancer and some cases of high-risk, localized disease. This is only palliative, however, since castration-recurrent disease typically occurs. Accordingly, intense research efforts focus upon achieving a better understanding of the cellular and molecular responses to androgen ablation and their roles in facilitating the transition to recurrence. In this chapter, we discuss how diminished androgen receptor (AR) signaling represents the pivotal mediator of a tightly coordinated signaling response that manifests in loss of AR expression, growth arrest, neuroendocrine differentiation (NED), and survival. Classic androgen-deprivation therapy has evolved to include approaches aimed at achieving complete suppression of AR signaling through the utilization of AR antagonists and inhibitors of androgen metabolism. This mediates repression of AR function at multiple levels by abrogating its transcriptional activity, increasing its turnover, and reducing translation of its transcript. Consequently, this leads to cellular trans-differentiation from an epithelial to neuroendocrine phenotype. NED cells figure critically in disease progression by virtue of secreting growth-promoting neurotrophic factors, possessing features of cancer stem cells, and surviving in the absence of androgen. Along these lines, phosphatidylinositol-3 kinase (PI3K)-Akt signaling is hyperactivated in response to androgen ablation and functions as a dominant antiapoptotic pathway, especially in the context of PTEN-mutant cancers such as LNCaP. Interestingly, mammalian target of rapamycin (mTOR) is implicated as a critical sensor of androgen signaling and an integrator of androgen ablation-induced AR down-regulation, PI3K-Akt hyperactivation, and NED. The marked effects of androgen ablation are due in large part to widespread changes in AR-regulated gene expression which produce a diagnostic androgen withdrawal expression signature. Although not well defined, we discuss potential mechanisms and gene product interactions that might explain how these translate into the molecular and biological features of androgen ablation.

Keywords

Androgen Receptor LNCaP Cell Androgen Receptor Expression Androgen Receptor Gene Neuroendocrine Differentiation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Agus, D.B., Cordon-Cardo, C., Fox, W., Drobnjak, M., Koff, A., Golde, D.W. & Scher, H.I. Prostate cancer cell cycle regulators: response to androgen withdrawal and development of androgen independence. Journal of the National Cancer Institute 91, 1869–1876 (1999).PubMedGoogle Scholar
  2. Ahuja, R., Pinyol, R., Reichenbach, N., Custer, L., Klingensmith, J., Kessels, M.M. & Qualmann, B. Cordon-bleu is an actin nucleation factor and controls neuronal morphology. Cell 131, 337–350 (2007).PubMedGoogle Scholar
  3. Allen, T., van Tuyl, M., Iyengar, P., Jothy, S., Post, M., Tsao, M.S. & Lobe, C.G. Grg1 acts as a lung-specific oncogene in a transgenic mouse model. Cancer Research 66, 1294–1301 (2006).PubMedGoogle Scholar
  4. Amler, L.C., Agus, D.B., LeDuc, C., Sapinoso, M.L., Fox, W.D., Kern, S., Lee, D., Wang, V., Leysens, M., Higgins, B., Martin, J., Gerald, W., Dracopoli, N., Cordon-Cardo, C., Scher, H.I. & Hampton, G.M. Dysregulated expression of androgen-responsive and nonresponsive genes in the androgen-independent prostate cancer xenograft model CWR22-R1. Cancer Research 60, 6134–6141 (2000).PubMedGoogle Scholar
  5. Assou, S., Le Carrour, T., Tondeur, S., Strom, S., Gabelle, A., Marty, S., Nadal, L., Pantesco, V., Reme, T., Hugnot, J.P., Gasca, S., Hovatta, O., Hamamah, S., Klein, B. & De Vos, J. A meta-analysis of human embryonic stem cells transcriptome integrated into a web-based expression atlas. Stem Cells 25, 961–973 (2007).PubMedGoogle Scholar
  6. Baarends, W.M., Themmen, A.P., Blok, L.J., Mackenbach, P., Brinkmann, A.O., Meijer, D., Faber, P.W., Trapman, J. & Grootegoed, J.A. The rat androgen receptor gene promoter. Molecular and Cellular Endocrinology 74, 75–84 (1990).PubMedGoogle Scholar
  7. Bakker, W.J., Harris, I.S. & Mak, T.W. FOXO3a is activated in response to hypoxic stress and inhibits HIF1-induced apoptosis via regulation of CITED2. Molecular Cell 28, 941–953 (2007a).Google Scholar
  8. Bakker, W.J., van Dijk, T.B., Parren-van Amelsvoort, M., Kolbus, A., Yamamoto, K., Steinlein, P., Verhaak, R.G., Mak, T.W., Beug, H., Lowenberg, B. & von Lindern, M. Differential regulation of Foxo3a target genes in erythropoiesis. Molecular and Cellular Biology 27, 3839–3854 (2007b).Google Scholar
  9. Ballinger, C.A., Connell, P., Wu, Y., Hu, Z., Thompson, L.J., Yin, L.Y. & Patterson, C. Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions. Molecular and Cellular Biology 19, 4535–4545 (1999).PubMedGoogle Scholar
  10. Banerjee, P.P., Banerjee, S., Tilly, K.I., Tilly, J.L., Brown, T.R. & Zirkin, B.R. Lobe-specific apoptotic cell death in rat prostate after androgen ablation by castration. Endocrinology 136, 4368–4376 (1995).PubMedGoogle Scholar
  11. Banerjee, S., Banerjee, P.P. & Brown, T.R. Castration-induced apoptotic cell death in the Brown Norway rat prostate decreases as a function of age. Endocrinology 141, 821–832 (2000).PubMedGoogle Scholar
  12. Banerjee, P.P., Banerjee, S. & Brown, T.R. Bcl-2 protein expression correlates with cell survival and androgen independence in rat prostatic lobes. Endocrinology 143, 1825–1832 (2002).PubMedGoogle Scholar
  13. Bang, Y.J., Pirnia, F., Fang, W.G., Kang, W.K., Sartor, O., Whitesell, L., Ha, M.J., Tsokos, M., Sheahan, M.D., Nguyen, P., Niklinski, W.T., Myers, C.E. & Trepel, J.B. Terminal neuroendocrine differentiation of human prostate carcinoma cells in response to increased intracellular cyclic AMP. Proceedings of the National Academy of Sciences of the United States of America 91, 5330–5334 (1994).PubMedGoogle Scholar
  14. Barbaro, V., Testa, A., Di Iorio, E., Mavilio, F., Pellegrini, G. & De Luca, M. C/EBPdelta regulates cell cycle and self-renewal of human limbal stem cells. The Journal of Cell Biology 177, 1037–1049 (2007).PubMedGoogle Scholar
  15. Belanger, A., Hum, D.W., Beaulieu, M., Levesque, E., Guillemette, C., Tchernof, A., Belanger, G., Turgeon, D. & Dubois, S. Characterization and regulation of UDP-glucuronosyltransferases in steroid target tissues. The Journal of Steroid Biochemistry and Molecular Biology 65, 301–310 (1998).PubMedGoogle Scholar
  16. Berchem, G.J., Bosseler, M., Sugars, L.Y., Voeller, H.J., Zeitlin, S. & Gelmann, E.P. Androgens induce resistance to bcl-2-mediated apoptosis in LNCaP prostate cancer cells. Cancer Research 55, 735–738 (1995).PubMedGoogle Scholar
  17. Berges, R.R., Furuya, Y., Remington, L., English, H.F., Jacks, T. & Isaacs, J.T. Cell proliferation, DNA repair, and p53 function are not required for programmed death of prostatic glandular cells induced by androgen ablation. Proceedings of the National Academy of Sciences of the United States of America 90, 8910–8914 (1993).PubMedGoogle Scholar
  18. Berquin, I.M., Min, Y., Wu, R., Wu, H. & Chen, Y.Q. Expression signature of the mouse prostate. The Journal of Biological Chemistry 280, 36442–36451 (2005).PubMedGoogle Scholar
  19. Bhatia-Gaur, R., Donjacour, A.A., Sciavolino, P.J., Kim, M., Desai, N., Young, P., Norton, C.R., Gridley, T., Cardiff, R.D., Cunha, G.R., Abate-Shen, C. & Shen, M.M. Roles for Nkx3.1 in prostate development and cancer. Genes Development 13, 966–977 (1999).PubMedGoogle Scholar
  20. Bieberich, C.J., Fujita, K., He, W.W. & Jay, G. Prostate-specific and androgen-dependent expression of a novel homeobox gene. The Journal of Biological Chemistry 271, 31779–31782 (1996).PubMedGoogle Scholar
  21. Boccardo, F., Rubagotti, A., Battaglia, M., Zattoni, F., Bertaccini, A., Romagnoli, A. & Conti, G. Influence of bicalutamide with or without tamoxifen or anastrozole on insulin-like growth factor 1 and binding proteins in prostate cancer patients. International Journal of Biological Markers 21, 123–126 (2006).PubMedGoogle Scholar
  22. Bowen, C., Bubendorf, L., Voeller, H.J., Slack, R., Willi, N., Sauter, G., Gasser, T.C., Koivisto, P., Lack, E.E., Kononen, J., Kallioniemi, O.P. & Gelmann, E.P. Loss of NKX3.1 expression in human prostate cancers correlates with tumor progression. Cancer Research 60, 6111–6115 (2000).PubMedGoogle Scholar
  23. Brandstrom, A., Westin, P., Bergh, A., Cajander, S. & Damber, J.E. Castration induces apoptosis in the ventral prostate but not in an androgen-sensitive prostatic adenocarcinoma in the rat. Cancer Research 54, 3594–3601 (1994).PubMedGoogle Scholar
  24. Brodin, G., ten Dijke, P., Funa, K., Heldin, C.H. & Landstrom, M. Increased smad expression and activation are associated with apoptosis in normal and malignant prostate after castration. Cancer Research 59, 2731–2738 (1999).PubMedGoogle Scholar
  25. Bubley, G.J., Carducci, M., Dahut, W., Dawson, N., Daliani, D., Eisenberger, M., Figg, W.D., Freidlin, B., Halabi, S., Hudes, G., Hussain, M., Kaplan, R., Myers, C., Oh, W., Petrylak, D.P., Reed, E., Roth, B., Sartor, O., Scher, H., Simons, J., Sinibaldi, V., Small, E.J., Smith, M.R., Trump, D.L., Wilding, G. & et al. Eligibility and response guidelines for phase II clinical trials in androgen-independent prostate cancer: recommendations from the Prostate-Specific Antigen Working Group. Journal of Clinical Oncology 17, 3461–3467 (1999).PubMedGoogle Scholar
  26. Bubulya, A., Wise, S.C., Shen, X.Q., Burmeister, L.A. & Shemshedini, L. c-Jun can mediate androgen receptor-induced transactivation. The Journal of Biological Chemistry 271, 24583–24589 (1996).PubMedGoogle Scholar
  27. Bubulya, A., Chen, S.Y., Fisher, C.J., Zheng, Z., Shen, X.Q. & Shemshedini, L. c-Jun potentiates the functional interaction between the amino and carboxyl termini of the androgen receptor. The Journal of Biological Chemistry 276, 44704–44711 (2001).PubMedGoogle Scholar
  28. Burchardt, T., Burchardt, M., Chen, M.W., Cao, Y., de la Taille, A., Shabsigh, A., Hayek, O., Dorai, T. & Buttyan, R. Transdifferentiation of prostate cancer cells to a neuroendocrine cell phenotype in vitro and in vivo. The Journal of Urology 162, 1800–1805 (1999).PubMedGoogle Scholar
  29. Camandola, S. & Mattson, M.P. Pro-apoptotic action of PAR-4 involves inhibition of NF-kappaB activity and suppression of BCL-2 expression. Journal of Neuroscience Research 61, 134–139 (2000).PubMedGoogle Scholar
  30. Cao, W., Liu, N., Tang, S., Bao, L., Shen, L., Yuan, H., Zhao, X. & Lu, H. Acetyl-Coenzyme A acyltransferase 2 attenuates the apoptotic effects of BNIP3 in two human cell lines. Biochimica et Biophysica Acta (2008).Google Scholar
  31. Carroll, E.A., Gerrelli, D., Gasca, S., Berg, E., Beier, D.R., Copp, A.J. & Klingensmith, J. Cordon-bleu is a conserved gene involved in neural tube formation. Developmental Biology 262, 16–31 (2003).PubMedGoogle Scholar
  32. Catz, S.D. & Johnson, J.L. Transcriptional regulation of bcl-2 by nuclear factor kappa B and its significance in prostate cancer. Oncogene 20, 7342–7351 (2001).PubMedGoogle Scholar
  33. Chadli, A., Bouhouche, I., Sullivan, W., Stensgard, B., McMahon, N., Catelli, M.G. & Toft, D.O. Dimerization and N-terminal domain proximity underlie the function of the molecular chaperone heat shock protein 90. Proceedings of the National Academy of Sciences of the United States of America 97, 12524–12529 (2000).PubMedGoogle Scholar
  34. Cheema, S.K., Mishra, S.K., Rangnekar, V.M., Tari, A.M., Kumar, R. & Lopez-Berestein, G. Par-4 transcriptionally regulates Bcl-2 through a WT1-binding site on the bcl-2 promoter. The Journal of Biological Chemistry 278, 19995–20005 (2003).PubMedGoogle Scholar
  35. Chen, C.D., Welsbie, D.S., Tran, C., Baek, S.H., Chen, R., Vessella, R., Rosenfeld, M.G. & Sawyers, C.L. Molecular determinants of resistance to antiandrogen therapy. Nature Medicine 10, 33–39 (2004).PubMedGoogle Scholar
  36. Chendil, D., Das, A., Dey, S., Mohiuddin, M. & Ahmed, M.M. Par-4, a pro-apoptotic gene, inhibits radiation-induced NF kappa B activity and Bcl-2 expression leading to induction of radiosensitivity in human prostate cancer cells PC-3. Cancer Biology and Therapy 1, 152–160 (2002).PubMedGoogle Scholar
  37. Chen, S., Sullivan, W.P., Toft, D.O. & Smith, D.F. Differential interactions of p23 and the TPR-containing proteins Hop, Cyp40, FKBP52 and FKBP51 with Hsp90 mutants. Cell Stress Chaperones 3, 118–129 (1998).PubMedGoogle Scholar
  38. Chen, X., Thakkar, H., Tyan, F., Gim, S., Robinson, H., Lee, C., Pandey, S.K., Nwokorie, C., Onwudiwe, N. & Srivastava, R.K. Constitutively active Akt is an important regulator of TRAIL sensitivity in prostate cancer. Oncogene 20, 6073–6083 (2001).PubMedGoogle Scholar
  39. Chiao, J.W., Hsieh, T.C., Xu, W., Sklarew, R.J. & Kancherla, R. Development of human prostate cancer cells to neuroendocrine-like cells by interleukin-1. International Journal of Oncology 15, 1033–1037 (1999).PubMedGoogle Scholar
  40. Chmelar, R., Buchanan, G., Need, E.F., Tilley, W. & Greenberg, N.M. Androgen receptor coregulators and their involvement in the development and progression of prostate cancer. International Journal of cancer 120, 719–733 (2007).Google Scholar
  41. Chouinard, S., Barbier, O. & Belanger, A. UDP-glucuronosyltransferase 2B15 (UGT2B15) and UGT2B17 enzymes are major determinants of the androgen response in prostate cancer LNCaP cells. The Journal of Biological Chemistry 282, 33466–33474 (2007).PubMedGoogle Scholar
  42. Chung, B.C., Picado-Leonard, J., Haniu, M., Bienkowski, M., Hall, P.F., Shively, J.E. & Miller, W.L. Cytochrome P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase): cloning of human adrenal and testis cDNAs indicates the same gene is expressed in both tissues. Proceedings of the National Academy of Sciences of the United States of America 84, 407–411 (1987).PubMedGoogle Scholar
  43. Cinar, B., De Benedetti, A. & Freeman, M.R. Post-transcriptional regulation of the androgen receptor by Mammalian target of rapamycin. Cancer Research 65, 2547–2553 (2005).PubMedGoogle Scholar
  44. Cockshott, I.D., Cooper, K.J., Sweetmore, D.S., Blacklock, N.J. & Denis, L. The pharmacokinetics of Casodex in prostate cancer patients after single and during multiple dosing. European Urology 18 Suppl 3, 10–17 (1990).PubMedGoogle Scholar
  45. Connell, P., Ballinger, C.A., Jiang, J., Wu, Y., Thompson, L.J., Hohfeld, J. & Patterson, C. The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. Nature Cell Biology 3, 93–96 (2001).PubMedGoogle Scholar
  46. Cornforth, A.N., Davis, J.S., Khanifar, E., Nastiuk, K.L., & Krolewski, J.J. FOXO3a mediates the androgen-dependent regulation of FLIP and contributes to TRAIL-induced apoptosis of LNCaP cells. Oncogene (2008).Google Scholar
  47. Cox, M.E., Deeble, P.D., Bissonette, E.A. & Parsons, S.J. Activated 3′,5′-cyclic AMP-dependent protein kinase is sufficient to induce neuroendocrine-like differentiation of the LNCaP prostate tumor cell line. The Journal of biological chemistry 275, 13812–13818 (2000).PubMedGoogle Scholar
  48. Daniels, D.L. & Weis, W.I. Beta-catenin directly displaces Groucho/TLE repressors from Tcf/Lef in Wnt-mediated transcription activation. Nature Structural & Molecular Biology 12, 364–371 (2005).Google Scholar
  49. De Coster, R., Wouters, W. & Bruynseels, J. P450-dependent enzymes as targets for prostate cancer therapy. The Journal of Steroid Biochemistry and Molecular Biology 56, 133–143 (1996).PubMedGoogle Scholar
  50. Dehni, G., Liu, Y., Husain, J. & Stifani, S. TLE expression correlates with mouse embryonic segmentation, neurogenesis, and epithelial determination. Mechanisms of Development 53, 369–381 (1995).PubMedGoogle Scholar
  51. de la Taille, A., Chen, M.W., Shabsigh, A., Bagiella, E., Kiss, A. & Buttyan, R. Fas antigen/CD-95 upregulation and activation during castration-induced regression of the rat ventral prostate gland. The Prostate 40, 89–96 (1999).PubMedGoogle Scholar
  52. Desai, K.V., Michalowska, A.M., Kondaiah, P., Ward, J.M., Shih, J.H. & Green, J.E. Gene expression profiling identifies a unique androgen-mediated inflammatory/immune signature and a PTEN (phosphatase and tensin homolog deleted on chromosome 10)-mediated apoptotic response specific to the rat ventral prostate. Molecular Endocrinology (Baltimore, Md 18, 2895–2907 (2004).Google Scholar
  53. Desai, S.J., Tepper, C.G. & Kung, H.J. Neuroendocrine differentiation and androgen independence in prostate cancer. in Prostate Cancer: Basic Mechanisms and Therapeutic Approaches (ed. Chang, C.) 157–190 (World Scientific, Singapore, 2005).Google Scholar
  54. di Sant'Agnese, P.A. Neuroendocrine differentiation in human prostatic carcinoma. Human Pathology 23, 287–296 (1992).PubMedGoogle Scholar
  55. Doll, J.A., Stellmach, V.M., Bouck, N.P., Bergh, A.R., Lee, C., Abramson, L.P., Cornwell, M.L., Pins, M.R., Borensztajn, J. & Crawford, S.E. Pigment epithelium-derived factor regulates the vasculature and mass of the prostate and pancreas. Nature Medicine 9, 774–780 (2003).PubMedGoogle Scholar
  56. Doniger, S.W., Salomonis, N., Dahlquist, K.D., Vranizan, K., Lawlor, S.C. & Conklin, B.R. MAPPFinder: using Gene Ontology and GenMAPP to create a global gene-expression profile from microarray data. Genome Biology 4, R7 (2003).PubMedGoogle Scholar
  57. Faber, P.W., van Rooij, H.C., Schipper, H.J., Brinkmann, A.O. & Trapman, J. Two different, overlapping pathways of transcription initiation are active on the TATA-less human androgen receptor promoter. The role of Sp1. The Journal of Biological Chemistry 268, 9296–9301 (1993).PubMedGoogle Scholar
  58. Fang, P., Hwa, V., Little, B.M. & Rosenfeld, R.G. IGFBP-3 sensitizes prostate cancer cells to interferon-gamma-induced apoptosis. Growth Hormone and IGF Research 18, 38–46 (2008).PubMedGoogle Scholar
  59. Fan, W., Yanase, T., Morinaga, H., Okabe, T., Nomura, M., Daitoku, H., Fukamizu, A., Kato, S., Takayanagi, R. & Nawata, H. Insulin-like growth factor 1/insulin signaling activates androgen signaling through direct interactions of Foxo1 with androgen receptor. The Journal of Biological Chemistry 282, 7329–7338 (2007).PubMedGoogle Scholar
  60. Febbo, P.G., Lowenberg, M., Thorner, A.R., Brown, M., Loda, M. & Golub, T.R. Androgen mediated regulation and functional implications of fkbp51 expression in prostate cancer. The Journal of Urology 173, 1772–1777 (2005).PubMedGoogle Scholar
  61. Franck-Lissbrant, I., Haggstrom, S., Damber, J.E. & Bergh, A. Testosterone stimulates angiogenesis and vascular regrowth in the ventral prostate in castrated adult rats. Endocrinology 139, 451–456 (1998).PubMedGoogle Scholar
  62. Frigo, D.E. & McDonnell, D.P. Differential effects of prostate cancer therapeutics on neuroendocrine transdifferentiation. Molecular Cancer Therapeutics 7, 659–669 (2008).PubMedGoogle Scholar
  63. Fujitani, M., Yamagishi, S., Che, Y.H., Hata, K., Kubo, T., Ino, H., Tohyama, M. & Yamashita, T. P311 accelerates nerve regeneration of the axotomized facial nerve. Journal of Neurochemistry 91, 737–744 (2004).PubMedGoogle Scholar
  64. Furutani, T., Watanabe, T., Tanimoto, K., Hashimoto, T., Koutoku, H., Kudoh, M., Shimizu, Y., Kato, S. & Shikama, H. Stabilization of androgen receptor protein is induced by agonist, not by antagonists. Biochemical and Biophysical Research Communications 294, 779–784 (2002).PubMedGoogle Scholar
  65. Garnick, M.B. Leuprolide versus diethylstilbestrol for previously untreated stage D2 prostate cancer. Results of a prospectively randomized trial. Urology 27, 21–28 (1986).PubMedGoogle Scholar
  66. Gaubert, C.M., Tremblay, R.R. & Dube, J.Y. Effect of sodium molybdate on cytosolic androgen receptors in rat prostate. Journal of Steroid Biochemistry 13, 931–937 (1980).PubMedGoogle Scholar
  67. Geller, J. Rationale for blockade of adrenal as well as testicular androgens in the treatment of advanced prostate cancer. Seminars in Oncology 12, 28–35 (1985).PubMedGoogle Scholar
  68. Georget, V., Terouanne, B., Nicolas, J.C. & Sultan, C. Mechanism of antiandrogen action: key role of hsp90 in conformational change and transcriptional activity of the androgen receptor. Biochemistry 41, 11824–11831 (2002).PubMedGoogle Scholar
  69. Gleave, M.E., Miyake, H., Zellweger, T., Chi, K., July, L., Nelson, C. & Rennie, P. Use of antisense oligonucleotides targeting the antiapoptotic gene, clusterin/testosterone-repressed prostate message 2, to enhance androgen sensitivity and chemosensitivity in prostate cancer. Urology 58, 39–49 (2001).PubMedGoogle Scholar
  70. Goswami, A., Burikhanov, R., de Thonel, A., Fujita, N., Goswami, M., Zhao, Y., Eriksson, J.E., Tsuruo, T. & Rangnekar, V.M. Binding and phosphorylation of par-4 by akt is essential for cancer cell survival. Molecular Cell 20, 33–44 (2005).PubMedGoogle Scholar
  71. Graff, J.R., Konicek, B.W., McNulty, A.M., Wang, Z., Houck, K., Allen, S., Paul, J.D., Hbaiu, A., Goode, R.G., Sandusky, G.E., Vessella, R.L. & Neubauer, B.L. Increased AKT activity contributes to prostate cancer progression by dramatically accelerating prostate tumor growth and diminishing p27Kip1 expression. The Journal of Biological Chemistry 275, 24500–24505 (2000).PubMedGoogle Scholar
  72. Grbavec, D. & Stifani, S. Molecular interaction between TLE1 and the carboxyl-terminal domain of HES-1 containing the WRPW motif. Biochemical and Biophysical Research Communications 223, 701–705 (1996).PubMedGoogle Scholar
  73. Gregory, C.W., Johnson, R.T., Jr., Mohler, J.L., French, F.S. & Wilson, E.M. Androgen receptor stabilization in recurrent prostate cancer is associated with hypersensitivity to low androgen. Cancer Research 61, 2892–2898 (2001).PubMedGoogle Scholar
  74. Grignon, D.J. & Sakr, W.A. Zonal origin of prostatic adenocarcinoma: are there biologic differences between transition zone and peripheral zone adenocarcinomas of the prostate gland? Journal of Cellular Biochemistry. Supplement 19, 267–269 (1994).PubMedGoogle Scholar
  75. Grigoryev, D.N., Long, B.J., Nnane, I.P., Njar, V.C., Liu, Y. & Brodie, A.M. Effects of new 17alpha-hydroxylase/C(17,20)-lyase inhibitors on LNCaP prostate cancer cell growth in vitro and in vivo. British Journal of Cancer 81, 622–630 (1999).PubMedGoogle Scholar
  76. Guillemette, C., Levesque, E., Beaulieu, M., Turgeon, D., Hum, D.W. & Belanger, A. Differential regulation of two uridine diphospho-glucuronosyltransferases, UGT2B15 and UGT2B17, in human prostate LNCaP cells. Endocrinology 138, 2998–3005 (1997).PubMedGoogle Scholar
  77. Gutman, A.B. & Gutman, E.B. An “ Acid ” Phosphatase Occurring in the Serum of Patients with Metastasizing Carcinoma of the Prostate Gland. The Journal of Clinical Investigation 17, 473–478 (1938).PubMedGoogle Scholar
  78. Hadaschik, B.A. & Gleave, M.E. Therapeutic options for hormone-refractory prostate cancer in 2007. Urologic Oncology 25, 413–419 (2007).PubMedGoogle Scholar
  79. Harrington, L.S., Findlay, G.M., Gray, A., Tolkacheva, T., Wigfield, S., Rebholz, H., Barnett, J., Leslie, N.R., Cheng, S., Shepherd, P.R., Gout, I., Downes, C.P. & Lamb, R.F. The TSC1–2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. The Journal of Cell Biology 166, 213–223 (2004).PubMedGoogle Scholar
  80. He, B., Bai, S., Hnat, A.T., Kalman, R.I., Minges, J.T., Patterson, C. & Wilson, E.M. An androgen receptor NH2-terminal conserved motif interacts with the COOH terminus of the Hsp70-interacting protein (CHIP). The Journal of Biological Chemistry 279, 30643–30653 (2004).PubMedGoogle Scholar
  81. Hieronymus, H., Lamb, J., Ross, K.N., Peng, X.P., Clement, C., Rodina, A., Nieto, M., Du, J., Stegmaier, K., Raj, S.M., Maloney, K.N., Clardy, J., Hahn, W.C., Chiosis, G. & Golub, T.R. Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators. Cancer cell 10, 321–330 (2006).PubMedGoogle Scholar
  82. Hirano, D., Okada, Y., Minei, S., Takimoto, Y. & Nemoto, N. Neuroendocrine differentiation in hormone refractory prostate cancer following androgen deprivation therapy. European Urology 45, 586–592; discussion 592 (2004).PubMedGoogle Scholar
  83. Hitchins, M.P., Bentley, L., Monk, D., Beechey, C., Peters, J., Kelsey, G., Ishino, F., Preece, M.A., Stanier, P. & Moore, G.E. DDC and COBL, flanking the imprinted GRB10 gene on 7p12, are biallelically expressed. Mammalian Genome 13, 686–691 (2002).PubMedGoogle Scholar
  84. Hodgson, M.C., Astapova, I., Hollenberg, A.N. & Balk, S.P. Activity of androgen receptor antagonist bicalutamide in prostate cancer cells is independent of NCoR and SMRT corepressors. Cancer Research 67, 8388–8395 (2007).PubMedGoogle Scholar
  85. Hsieh, J.T., Wu, H.C., Gleave, M.E., von Eschenbach, A.C. & Chung, L.W. Autocrine regulation of prostate-specific antigen gene expression in a human prostatic cancer (LNCaP) subline. Cancer Research 53, 2852–2857 (1993).PubMedGoogle Scholar
  86. Huang, C.Y., Beliakoff, J., Li, X., Lee, J., Sharma, M., Lim, B. & Sun, Z. hZimp7, a novel PIAS-like protein, enhances androgen receptor-mediated transcription and interacts with SWI/SNF-like BAF complexes. Molecular Endocrinology (Baltimore, Md) 19, 2915–2929 (2005).Google Scholar
  87. Huggins, C. & Hodges, C.V. Studies of prostatic cancer: I. Effect of castration, estrogen and androgen injections on serum phosphatases in metastatic carcinoma of the prostate. Cancer Research 1, 293–307 (1941).Google Scholar
  88. Huggins, C., Stevens, R.E. & Hodges, C.V. Studies on prostate cancer: II. The effect of castration on advanced carcinoma of the prostate gland. Archives of Surgery 43, 209 (1941).Google Scholar
  89. Huss, W.J., Gregory, C.W. & Smith, G.J. Neuroendocrine cell differentiation in the CWR22 human prostate cancer xenograft: association with tumor cell proliferation prior to recurrence. The Prostate 60, 91–97 (2004).PubMedGoogle Scholar
  90. Ito, T., Yamamoto, S., Ohno, Y., Namiki, K., Aizawa, T., Akiyama, A. & Tachibana, M. Up-regulation of neuroendocrine differentiation in prostate cancer after androgen deprivation therapy, degree and androgen independence. Oncology Reports 8, 1221–1224 (2001).PubMedGoogle Scholar
  91. Jarriault, S., Brou, C., Logeat, F., Schroeter, E.H., Kopan, R. & Israel, A. Signalling downstream of activated mammalian Notch. Nature 377, 355–358 (1995).PubMedGoogle Scholar
  92. Jiang, J., Ballinger, C.A., Wu, Y., Dai, Q., Cyr, D.M., Hohfeld, J. & Patterson, C. CHIP is a U-box-dependent E3 ubiquitin ligase: identification of Hsc70 as a target for ubiquitylation. The Journal of Biological Chemistry 276, 42938–42944 (2001).PubMedGoogle Scholar
  93. Johansson, A., Jones, J., Pietras, K., Kilter, S., Skytt, A., Rudolfsson, S.H. & Bergh, A. A stroma targeted therapy enhances castration effects in a transplantable rat prostate cancer model. The Prostate 67, 1664–1676 (2007).PubMedGoogle Scholar
  94. Johnson, J.L. & Toft, D.O. A novel chaperone complex for steroid receptors involving heat shock proteins, immunophilins, and p23. The Journal of Biological Chemistry 269, 24989–24993 (1994).PubMedGoogle Scholar
  95. Jongsma, J., Oomen, M.H., Noordzij, M.A., Van Weerden, W.M., Martens, G.J., van der Kwast, T.H., Schroder, F.H. & van Steenbrugge, G.J. Kinetics of neuroendocrine differentiation in an androgen-dependent human prostate xenograft model. The American Journal of Pathology 154, 543–551 (1999).PubMedGoogle Scholar
  96. Jongsma, J., Oomen, M.H., Noordzij, M.A., Van Weerden, W.M., Martens, G.J., van der Kwast, T.H., Schroder, F.H. & van Steenbrugge, G.J. Androgen deprivation of the PC-310 [correction of prohormone convertase-310] human prostate cancer model system induces neuroendocrine differentiation. Cancer Research 60, 741–748 (2000).PubMedGoogle Scholar
  97. Jongsma, J., Oomen, M.H., Noordzij, M.A., Van Weerden, W.M., Martens, G.J., van der Kwast, T.H., Schroder, F.H. & van Steenbrugge, G.J. Different profiles of neuroendocrine cell differentiation evolve in the PC-310 human prostate cancer model during long-term androgen deprivation. The Prostate 50, 203–215 (2002).PubMedGoogle Scholar
  98. Joseph, I.B., Nelson, J.B., Denmeade, S.R. & Isaacs, J.T. Androgens regulate vascular endothelial growth factor content in normal and malignant prostatic tissue. Clinical Cancer Research 3, 2507–2511 (1997).PubMedGoogle Scholar
  99. July, L.V., Akbari, M., Zellweger, T., Jones, E.C., Goldenberg, S.L. & Gleave, M.E. Clusterin expression is significantly enhanced in prostate cancer cells following androgen withdrawal therapy. The Prostate 50, 179–188 (2002).PubMedGoogle Scholar
  100. Kaneda, N., Talukder, A.H., Nishiyama, H., Koizumi, S. & Muramatsu, T. Midkine, a heparin-binding growth/differentiation factor, exhibits nerve cell adhesion and guidance activity for neurite outgrowth in vitro. Journal of Biochemistry 119, 1150–1156 (1996).PubMedGoogle Scholar
  101. Kawano, Y., Yoshimura, T., Tsuboi, D., Kawabata, S., Kaneko-Kawano, T., Shirataki, H., Takenawa, T. & Kaibuchi, K. CRMP-2 is involved in kinesin-1-dependent transport of the Sra-1/WAVE1 complex and axon formation. Molecular and Cellular Biology 25, 9920–9935 (2005).PubMedGoogle Scholar
  102. Kemppainen, J.A., Lane, M.V., Sar, M. & Wilson, E.M. Androgen receptor phosphorylation, turnover, nuclear transport, and transcriptional activation. Specificity for steroids and antihormones. The Journal of Biological Chemistry 267, 968–974 (1992).PubMedGoogle Scholar
  103. Kerjan, G., Dolan, J., Haumaitre, C., Schneider-Maunoury, S., Fujisawa, H., Mitchell, K.J. & Chedotal, A. The transmembrane semaphorin Sema6A controls cerebellar granule cell migration. Nature Neuroscience 8, 1516–1524 (2005).PubMedGoogle Scholar
  104. Kerr, J.F. & Searle, J. Deletion of cells by apoptosis during castration-induced involution of the rat prostate. Virchows Archiv 13, 87–102 (1973).Google Scholar
  105. Kim, J., Adam, R.M. & Freeman, M.R. Activation of the Erk mitogen-activated protein kinase pathway stimulates neuroendocrine differentiation in LNCaP cells independently of cell cycle withdrawal and STAT3 phosphorylation. Cancer Research 62, 1549–1554 (2002).PubMedGoogle Scholar
  106. Kitagawa, Y., Dai, J., Zhang, J., Keller, J.M., Nor, J., Yao, Z. & Keller, E.T. Vascular endothelial growth factor contributes to prostate cancer-mediated osteoblastic activity. Cancer Research 65, 10921–10929 (2005).PubMedGoogle Scholar
  107. Kitamura, M., Buczko, E. & Dufau, M.L. Dissociation of hydroxylase and lyase activities by site-directed mutagenesis of the rat P45017 alpha. 5, 1373–1380 (1991).Google Scholar
  108. Klotz, L. & Schellhammer, P. Combined androgen blockade: the case for bicalutamide. Clinical Prostate Cancer 3, 215–219 (2005).PubMedGoogle Scholar
  109. Kobayashi, Y., Miwa, S., Merry, D.E., Kume, A., Mei, L., Doyu, M. & Sobue, G. Caspase-3 cleaves the expanded androgen receptor protein of spinal and bulbar muscular atrophy in a polyglutamine repeat length-dependent manner. Biochemical and Biophysical Research Communications 252, 145–150 (1998).PubMedGoogle Scholar
  110. Kojima, S., Mulholland, D.J., Ettinger, S., Fazli, L., Nelson, C.C. & Gleave, M.E. Differential regulation of IGFBP-3 by the androgen receptor in the lineage-related androgen-dependent LNCaP and androgen-independent C4–2 prostate cancer models. The Prostate 66, 971–986 (2006).PubMedGoogle Scholar
  111. Kokontis, J.M., Hay, N. & Liao, S. Progression of LNCaP prostate tumor cells during androgen deprivation: hormone-independent growth, repression of proliferation by androgen, and role for p27Kip1 in androgen-induced cell cycle arrest. Molecular Endocrinology (Baltimore, Md) 12, 941–953 (1998).Google Scholar
  112. Kondapaka, S.B., Singh, S.S., Dasmahapatra, G.P., Sausville, E.A. & Roy, K.K. Perifosine, a novel alkylphospholipid, inhibits protein kinase B activation. Molecular Cancer Therapeutics 2, 1093–1103 (2003).PubMedGoogle Scholar
  113. Kreisberg, J.I., Malik, S.N., Prihoda, T.J., Bedolla, R.G., Troyer, D.A., Kreisberg, S. & Ghosh, P.M. Phosphorylation of Akt (Ser473) is an excellent predictor of poor clinical outcome in prostate cancer. Cancer Research 64, 5232–5236 (2004).PubMedGoogle Scholar
  114. Krongrad, A., Wilson, C.M., Wilson, J.D., Allman, D.R. & McPhaul, M.J. Androgen increases androgen receptor protein while decreasing receptor mRNA in LNCaP cells. Molecular and Cellular Endocrinology 76, 79–88 (1991).PubMedGoogle Scholar
  115. Kuhn, J.M., Billebaud, T., Navratil, H., Moulonguet, A., Fiet, J., Grise, P., Louis, J.F., Costa, P., Husson, J.M., Dahan, R. & et al. Prevention of the transient adverse effects of a gonadotropin-releasing hormone analogue (buserelin) in metastatic prostatic carcinoma by administration of an antiandrogen (nilutamide). The New England Journal of Medicine 321, 413–418 (1989).PubMedGoogle Scholar
  116. Kurita, T., Wang, Y.Z., Donjacour, A.A., Zhao, C., Lydon, J.P., O'Malley, B.W., Isaacs, J.T., Dahiya, R. & Cunha, G.R. Paracrine regulation of apoptosis by steroid hormones in the male and female reproductive system. Cell Death and Differentiation 8, 192–200 (2001).PubMedGoogle Scholar
  117. Labrie, F. Medical castration with LHRH agonists: 25 years later with major benefits achieved on survival in prostate cancer. Journal of Andrology 25, 305–313 (2004).PubMedGoogle Scholar
  118. Lamb, J., Crawford, E.D., Peck, D., Modell, J.W., Blat, I.C., Wrobel, M.J., Lerner, J., Brunet, J.P., Subramanian, A., Ross, K.N., Reich, M., Hieronymus, H., Wei, G., Armstrong, S.A., Haggarty, S.J., Clemons, P.A., Wei, R., Carr, S.A., Lander, E.S. & Golub, T.R. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease. Science 313, 1929–1935 (2006).PubMedGoogle Scholar
  119. Landstrom, M., Damber, J.E. & Bergh, A. Prostatic tumor regrowth after initially successful castration therapy may be related to a decreased apoptotic cell death rate. Cancer Research 54, 4281–4284 (1994).PubMedGoogle Scholar
  120. Lawson, D.A., Xin, L., Lukacs, R.U., Cheng, D. & Witte, O.N. Isolation and functional characterization of murine prostate stem cells. Proceedings of the National Academy of Sciences of the United States of America 104, 181–186 (2007).PubMedGoogle Scholar
  121. Lee, C. Gross dissection of three lobes of the rat prostate. in Current Concepts and Approaches to the Study of Prostate Cancer (eds. Coffey, D.S., Bruchovsky, N., Gardner, W.A.J., Resnick, M. & Karr, J.P.) 577–582 (Alan R. Liss, Inc., New York, NY, 1987).Google Scholar
  122. Lee, H.J. & Chang, C. Recent advances in androgen receptor action. Cellular and Molecular Life Sciences 60, 1613–1622 (2003).PubMedGoogle Scholar
  123. Lee, K.W., Cobb, L.J., Paharkova-Vatchkova, V., Liu, B., Milbrandt, J. & Cohen, P. Contribution of the orphan nuclear receptor Nur77 to the apoptotic action of IGFBP-3. Carcinogenesis 28, 1653–1658 (2007).PubMedGoogle Scholar
  124. Lee, K.W., Ma, L., Yan, X., Liu, B., Zhang, X.K. & Cohen, P. Rapid apoptosis induction by IGFBP-3 involves an insulin-like growth factor-independent nucleomitochondrial translocation of RXRalpha/Nur77. The Journal of Biological Chemistry 280, 16942–16948 (2005).PubMedGoogle Scholar
  125. Lee, S.O., Chun, J.Y., Nadiminty, N., Lou, W. & Gao, A.C. Interleukin-6 undergoes transition from growth inhibitor associated with neuroendocrine differentiation to stimulator accompanied by androgen receptor activation during LNCaP prostate cancer cell progression. The Prostate 67, 764–773 (2007).PubMedGoogle Scholar
  126. Leighton, P.A., Mitchell, K.J., Goodrich, L.V., Lu, X., Pinson, K., Scherz, P., Skarnes, W.C. & Tessier-Lavigne, M. Defining brain wiring patterns and mechanisms through gene trapping in mice. Nature 410, 174–179 (2001).PubMedGoogle Scholar
  127. Li, J., Yen, C., Liaw, D., Podsypanina, K., Bose, S., Wang, S.I., Puc, J., Miliaresis, C., Rodgers, L., McCombie, R., Bigner, S.H., Giovanella, B.C., Ittmann, M., Tycko, B., Hibshoosh, H., Wigler, M.H. & Parsons, R. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275, 1943–1947 (1997).PubMedGoogle Scholar
  128. Li, R., Erdamar, S., Dai, H., Wheeler, T.M., Frolov, A., Scardino, P.T., Thompson, T.C. & Ayala, G.E. Forkhead protein FKHR and its phosphorylated form p-FKHR in human prostate cancer. Human Pathology 38, 1501–1507 (2007).PubMedGoogle Scholar
  129. Libertini, S.J., Tepper, C.G., Rodriguez, V., Asmuth, D.M., Kung, H.J. & Mudryj, M. Evidence for calpain-mediated androgen receptor cleavage as a mechanism for androgen independence. Cancer Research 67, 9001–9005 (2007).PubMedGoogle Scholar
  130. Limonta, P., Montagnani Marelli, M. & Moretti, R.M. LHRH analogues as anticancer agents: pituitary and extrapituitary sites of action. Expert Opinion on Investigational Drugs 10, 709–720 (2001).PubMedGoogle Scholar
  131. Lin, J., Adam, R.M., Santiestevan, E. & Freeman, M.R. The phosphatidylinositol 3′-kinase pathway is a dominant growth factor-activated cell survival pathway in LNCaP human prostate carcinoma cells. Cancer Research 59, 2891–2897 (1999).PubMedGoogle Scholar
  132. Lin, H.K., Yeh, S., Kang, H.Y. & Chang, C. Akt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor. Proceedings of the National Academy of Sciences of the United States of America 98, 7200–7205 (2001).PubMedGoogle Scholar
  133. Lin, H.K., Wang, L., Hu, Y.C., Altuwaijri, S. & Chang, C. Phosphorylation-dependent ubiquitylation and degradation of androgen receptor by Akt require Mdm2 E3 ligase. The EMBO Journal 21, 4037–4048 (2002).PubMedGoogle Scholar
  134. Lin, H.K., Hu, Y.C., Yang, L., Altuwaijri, S., Chen, Y.T., Kang, H.Y. & Chang, C. Suppression versus induction of androgen receptor functions by the phosphatidylinositol 3-kinase/Akt pathway in prostate cancer LNCaP cells with different passage numbers. The Journal of Biological Chemistry 278, 50902–50907 (2003).PubMedGoogle Scholar
  135. Lin, B., Kolluri, S.K., Lin, F., Liu, W., Han, Y.H., Cao, X., Dawson, M.I., Reed, J.C. & Zhang, X.K. Conversion of Bcl-2 from protector to killer by interaction with nuclear orphan receptor Nur77/TR3. Cell 116, 527–540 (2004).PubMedGoogle Scholar
  136. Link, K.A., Burd, C.J., Williams, E., Marshall, T., Rosson, G., Henry, E., Weissman, B. & Knudsen, K.E. BAF57 governs androgen receptor action and androgen-dependent proliferation through SWI/SNF. Molecular and Cellular Biology 25, 2200–2215 (2005).PubMedGoogle Scholar
  137. Liu, B., Lee, H.Y., Weinzimer, S.A., Powell, D.R., Clifford, J.L., Kurie, J.M. & Cohen, P. Direct functional interactions between insulin-like growth factor-binding protein-3 and retinoid X receptor-alpha regulate transcriptional signaling and apoptosis. The Journal of Biological Chemistry 275, 33607–33613 (2000).PubMedGoogle Scholar
  138. Liu, S., Vinall, R.L., Tepper, C., Shi, X.B., Xue, L.R., Ma, A.H., Wang, L.Y., Fitzgerald, L.D., Wu, Z., Gandour-Edwards, R., deVere White, R.W. & Kung, H.J. Inappropriate activation of androgen receptor by relaxin via beta-catenin pathway. Oncogene 27, 499–505 (2008).PubMedGoogle Scholar
  139. Louie, M.C., Yang, H.Q., Ma, A.H., Xu, W., Zou, J.X., Kung, H.J. & Chen, H.W. Androgen-induced recruitment of RNA polymerase II to a nuclear receptor-p160 coactivator complex. Proceedings of the National Academy of Sciences of the United States of America 100, 2226–2230 (2003).PubMedGoogle Scholar
  140. Lubahn, D.B., Joseph, D.R., Sar, M., Tan, J., Higgs, H.N., Larson, R.E., French, F.S. & Wilson, E.M. The human androgen receptor: complementary deoxyribonucleic acid cloning, sequence analysis and gene expression in prostate. Molecular Endocrinology (Baltimore, Md) 2, 1265–1275 (1988a).Google Scholar
  141. Lubahn, D.B., Joseph, D.R., Sullivan, P.M., Willard, H.F., French, F.S. & Wilson, E.M. Cloning of human androgen receptor complementary DNA and localization to the X chromosome. Science 240, 327–330 (1988b).Google Scholar
  142. Majumder, P.K., Febbo, P.G., Bikoff, R., Berger, R., Xue, Q., McMahon, L.M., Manola, J., Brugarolas, J., McDonnell, T.J., Golub, T.R., Loda, M., Lane, H.A. & Sellers, W.R. mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Nature Medicine 10, 594–601 (2004).PubMedGoogle Scholar
  143. Malik, S.N., Brattain, M., Ghosh, P.M., Troyer, D.A., Prihoda, T., Bedolla, R. & Kreisberg, J.I. Immunohistochemical demonstration of phospho-Akt in high Gleason grade prostate cancer. Clinical Cancer Research 8, 1168–1171 (2002).PubMedGoogle Scholar
  144. Maltepe, E., Keith, B., Arsham, A.M., Brorson, J.R. & Simon, M.C. The role of ARNT2 in tumor angiogenesis and the neural response to hypoxia. Biochemical and Biophysical Research Communications 273, 231–238 (2000).PubMedGoogle Scholar
  145. Maniatis, T., Goodbourn, S. & Fischer, J.A. Regulation of inducible and tissue-specific gene expression. Science 236, 1237–1245 (1987).PubMedGoogle Scholar
  146. Mason, H.A., Rakowiecki, S.M., Raftopoulou, M., Nery, S., Huang, Y., Gridley, T. & Fishell, G. Notch signaling coordinates the patterning of striatal compartments. Development 132, 4247–4258 (2005).PubMedGoogle Scholar
  147. Matsunaga, N., Kaku, T., Itoh, F., Tanaka, T., Hara, T., Miki, H., Iwasaki, M., Aono, T., Yamaoka, M., Kusaka, M. & Tasaka, A. C17,20-lyase inhibitors I. Structure-based de novo design and SAR study of C17,20-lyase inhibitors. Bioorganic and Medicinal Chemistry 12, 2251–2273 (2004).PubMedGoogle Scholar
  148. Matusik, R.J., Jin, R.J., Sun, Q., Wang, Y., Yu, X., Gupta, A., Nandana, S., Case, T.C., Paul, M., Mirosevich, J., Oottamasathien, S. & Thomas, J. Prostate epithelial cell fate. Differentiation 76, 682–698 (2008).PubMedGoogle Scholar
  149. McCollum, A.K., Teneyck, C.J., Sauer, B.M., Toft, D.O. & Erlichman, C. Up-regulation of heat shock protein 27 induces resistance to 17-allylamino-demethoxygeldanamycin through a glutathione-mediated mechanism. Cancer Research 66, 10967–10975 (2006).PubMedGoogle Scholar
  150. McDonough, W.S., Tran, N.L. & Berens, M.E. Regulation of glioma cell migration by serine-phosphorylated P311. Neoplasia (New York, NY) 7, 862–872 (2005).Google Scholar
  151. Michikawa, M., Kikuchi, S., Muramatsu, H., Muramatsu, T. & Kim, S.U. Retinoic acid responsive gene product, midkine, has neurotrophic functions for mouse spinal cord and dorsal root ganglion neurons in culture. Journal of Neuroscience Research 35, 530–539 (1993).PubMedGoogle Scholar
  152. Mizokami, A. & Chang, C. Induction of translation by the 5′-untranslated region of human androgen receptor mRNA. The Journal of Biological Chemistry 269, 25655–25659 (1994).PubMedGoogle Scholar
  153. Mizokami, A., Yeh, S.Y. & Chang, C. Identification of 3′,5′-cyclic adenosine monophosphate response element and other cis-acting elements in the human androgen receptor gene promoter. Molecular Endocrinology (Baltimore, Md) 8, 77–88 (1994).Google Scholar
  154. Modur, V., Nagarajan, R., Evers, B.M. & Milbrandt, J. FOXO proteins regulate tumor necrosis factor-related apoptosis inducing ligand expression. Implications for PTEN mutation in prostate cancer. The Journal of Biological Chemistry 277, 47928–47937 (2002).PubMedGoogle Scholar
  155. Mora, G.R., Prins, G.S. & Mahesh, V.B. Autoregulation of androgen receptor protein and messenger RNA in rat ventral prostate is protein synthesis dependent. The Journal of Steroid Biochemistry and Molecular Biology 58, 539–549 (1996).PubMedGoogle Scholar
  156. Mori, Y., Yin, J., Rashid, A., Leggett, B.A., Young, J., Simms, L., Kuehl, P.M., Langenberg, P., Meltzer, S.J. & Stine, O.C. Instabilotyping: comprehensive identification of frameshift mutations caused by coding region microsatellite instability. Cancer Research 61, 6046–6049 (2001).PubMedGoogle Scholar
  157. Mostaghel, E.A., Page, S.T., Lin, D.W., Fazli, L., Coleman, I.M., True, L.D., Knudsen, B., Hess, D.L., Nelson, C.C., Matsumoto, A.M., Bremner, W.J., Gleave, M.E. & Nelson, P.S. Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. Cancer Research 67, 5033–5041 (2007).PubMedGoogle Scholar
  158. Muramatsu, T. Midkine (MK), the product of a retinoic acid responsive gene, and pleiotrophin constitute a new protein family regulating growth and differentiation. The International Journal of Developmental Biology 37, 183–188 (1993).PubMedGoogle Scholar
  159. Muramatsu, H. & Muramatsu, T. Purification of recombinant midkine and examination of its biological activities: functional comparison of new heparin binding factors. Biochemical and Biophysical Research Communications 177, 652–658 (1991).PubMedGoogle Scholar
  160. Murillo, H., Huang, H., Schmidt, L.J., Smith, D.I. & Tindall, D.J. Role of PI3K signaling in survival and progression of LNCaP prostate cancer cells to the androgen refractory state. Endocrinology 142, 4795–4805 (2001).PubMedGoogle Scholar
  161. Nakajin, S., Shively, J.E., Yuan, P.M. & Hall, P.F. Microsomal cytochrome P-450 from neonatal pig testis: two enzymatic activities (17 alpha-hydroxylase and c17,20-lyase) associated with one protein. Biochemistry 20, 4037–4042 (1981).PubMedGoogle Scholar
  162. Nakaya, H.I., Beckedorff, F.C., Baldini, M.L., Fachel, A.A., Reis, E.M. & Verjovski-Almeida, S. Splice variants of TLE family genes and up-regulation of a TLE3 isoform in prostate tumors. Biochemical and Biophysical Research Communications 364, 918–923 (2007).PubMedGoogle Scholar
  163. Nelson, P.S., Clegg, N., Arnold, H., Ferguson, C., Bonham, M., White, J., Hood, L. & Lin, B. The program of androgen-responsive genes in neoplastic prostate epithelium. Proceedings of the National Academy of Sciences of the United States of America 99, 11890–11895 (2002).PubMedGoogle Scholar
  164. Neri, R., Peets, E. & Watnick, A. Anti-androgenicity of flutamide and its metabolite Sch 16423. Biochemical Society Transactions 7, 565–569 (1979).PubMedGoogle Scholar
  165. Nishiyama, T., Hashimoto, Y. & Takahashi, K. The influence of androgen deprivation therapy on dihydrotestosterone levels in the prostatic tissue of patients with prostate cancer. Clinical Cancer Research 10, 7121–7126 (2004).PubMedGoogle Scholar
  166. Oh, J., Woo, J.M., Choi, E., Kim, T., Cho, B.N., Park, Z.Y., Kim, Y.C., Kim, D.H. & Cho, C. Molecular, biochemical, and cellular characterization of epididymal ADAMs, ADAM7 and ADAM28. Biochemical and Biophysical Research Communications 331, 1374–1383 (2005).PubMedGoogle Scholar
  167. Owada, K., Sanjo, N., Kobayashi, T., Mizusawa, H., Muramatsu, H., Muramatsu, T. & Michikawa, M. Midkine inhibits caspase-dependent apoptosis via the activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase in cultured neurons. Journal of Neurochemistry 73, 2084–2092 (1999).PubMedGoogle Scholar
  168. Ozes, O.N., Mayo, L.D., Gustin, J.A., Pfeffer, S.R., Pfeffer, L.M. & Donner, D.B. NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase. Nature 401, 82–85 (1999).PubMedGoogle Scholar
  169. Palaparti, A., Baratz, A. & Stifani, S. The Groucho/transducin-like enhancer of split transcriptional repressors interact with the genetically defined amino-terminal silencing domain of histone H3. The Journal of Biological Chemistry 272, 26604–26610 (1997).PubMedGoogle Scholar
  170. Peeling, W.B. Phase III studies to compare goserelin (Zoladex) with orchiectomy and with diethylstilbestrol in treatment of prostatic carcinoma. Urology 33, 45–52 (1989).PubMedGoogle Scholar
  171. Pelley, R.P., Chinnakannu, K., Murthy, S., Strickland, F.M., Menon, M., Dou, Q.P., Barrack, E.R. & Reddy, G.P. Calmodulin-androgen receptor (AR) interaction: calcium-dependent, calpain-mediated breakdown of AR in LNCaP prostate cancer cells. Cancer Research 66, 11754–11762 (2006).PubMedGoogle Scholar
  172. Peng, L., Malloy, P.J., Wang, J. & Feldman, D. Growth inhibitory concentrations of androgens up-regulate insulin-like growth factor binding protein-3 expression via an androgen response element in LNCaP human prostate cancer cells. Endocrinology 147, 4599–4607 (2006).PubMedGoogle Scholar
  173. Perlman, H., Zhang, X., Chen, M.W., Walsh, K. & Buttyan, R. An elevated bax/bcl-2 ratio corresponds with the onset of prostate epithelial cell apoptosis. Cell Death and Differentiation 6, 48–54 (1999).PubMedGoogle Scholar
  174. Pinski, J., Wang, Q., Quek, M.L., Cole, A., Cooc, J., Danenberg, K. & Danenberg, P.V. Genistein-induced neuroendocrine differentiation of prostate cancer cells. The Prostate 66, 1136–1143 (2006).PubMedGoogle Scholar
  175. Pratt, W.B. & Toft, D.O. Steroid receptor interactions with heat shock protein and immunophilin chaperones. Endocrine Reviews 18, 306–360 (1997).PubMedGoogle Scholar
  176. Price, D. Comparative aspects of development and structure in the prostate. National Cancer Institute Monograph 12, 1–27 (1963).PubMedGoogle Scholar
  177. Prout, G.R., Jr., Kliman, B., Daly, J.J., Maclaughlin, R.A. & Griffin, P.P. In vitro uptake of 3H testosterone and its conversion to dihydrotestosterone by prostatic carcinoma and other tissues. The Journal of Urology 116, 603–610 (1976).PubMedGoogle Scholar
  178. Qiu, Y., Robinson, D., Pretlow, T.G. & Kung, H.J. Etk/Bmx, a tyrosine kinase with a pleckstrin-homology domain, is an effector of phosphatidylinositol 3′-kinase and is involved in interleukin 6-induced neuroendocrine differentiation of prostate cancer cells. Proceedings of the National Academy of Sciences of the United States of America 95, 3644–3649 (1998).PubMedGoogle Scholar
  179. Quarmby, V.E., Yarbrough, W.G., Lubahn, D.B., French, F.S. & Wilson, E.M. Autologous down-regulation of androgen receptor messenger ribonucleic acid. Molecular Endocrinology (Baltimore, Md) 4, 22–28 (1990).Google Scholar
  180. Raffo, A.J., Perlman, H., Chen, M.W., Day, M.L., Streitman, J.S. & Buttyan, R. Overexpression of bcl-2 protects prostate cancer cells from apoptosis in vitro and confers resistance to androgen depletion in vivo. Cancer Research 55, 4438–4445 (1995).PubMedGoogle Scholar
  181. Rajah, R., Valentinis, B. & Cohen, P. Insulin-like growth factor (IGF)-binding protein-3 induces apoptosis and mediates the effects of transforming growth factor-beta1 on programmed cell death through a p53- and IGF-independent mechanism. The Journal of Biological Chemistry 272, 12181–12188 (1997).PubMedGoogle Scholar
  182. Ramaswamy, S., Nakamura, N., Sansal, I., Bergeron, L. & Sellers, W.R. A novel mechanism of gene regulation and tumor suppression by the transcription factor FKHR. Cancer Cell 2, 81–91 (2002).PubMedGoogle Scholar
  183. Renaud, J., Kerjan, G., Sumita, I., Zagar, Y., Georget, V., Kim, D., Fouquet, C., Suda, K., Sanbo, M., Suto, F., Ackerman, S.L., Mitchell, K.J., Fujisawa, H. & Chedotal, A. Plexin-A2 and its ligand, Sema6A, control nucleus-centrosome coupling in migrating granule cells. Nature Neuroscience 11, 440–449 (2008).PubMedGoogle Scholar
  184. Renoir, J.M., Radanyi, C., Faber, L.E. & Baulieu, E.E. The non-DNA-binding heterooligomeric form of mammalian steroid hormone receptors contains a hsp90-bound 59-kilodalton protein. The Journal of Biological Chemistry 265, 10740–10745 (1990).PubMedGoogle Scholar
  185. Robinson, M.R. & Thomas, B.S. Effect of hormonal therapy on plasma testosterone levels in prostatic carcinoma. British Medical Journal 4, 391–394 (1971).PubMedGoogle Scholar
  186. Rocchi, P., So, A., Kojima, S., Signaevsky, M., Beraldi, E., Fazli, L., Hurtado-Coll, A., Yamanaka, K. & Gleave, M. Heat shock protein 27 increases after androgen ablation and plays a cytoprotective role in hormone-refractory prostate cancer. Cancer Research 64, 6595–6602 (2004).PubMedGoogle Scholar
  187. Rocchi, P., Beraldi, E., Ettinger, S., Fazli, L., Vessella, R.L., Nelson, C. & Gleave, M. Increased Hsp27 after androgen ablation facilitates androgen-independent progression in prostate cancer via signal transducers and activators of transcription 3-mediated suppression of apoptosis. Cancer Research 65, 11083–11093 (2005).PubMedGoogle Scholar
  188. Rokhlin, O.W., Guseva, N.V., Tagiyev, A.F., Glover, R.A. & Cohen, M.B. Caspase-8 activation is necessary but not sufficient for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in the prostatic carcinoma cell line LNCaP. The Prostate 52, 1–11 (2002).PubMedGoogle Scholar
  189. Romashkova, J.A. & Makarov, S.S. NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling. Nature 401, 86–90 (1999).PubMedGoogle Scholar
  190. Ryan, C.J. & Small, E.J. Early versus delayed androgen deprivation for prostate cancer: new fuel for an old debate. Journal of Clinical Oncology 23, 8225–8231 (2005).PubMedGoogle Scholar
  191. Sansone, P., Storci, G., Tavolari, S., Guarnieri, T., Giovannini, C., Taffurelli, M., Ceccarelli, C., Santini, D., Paterini, P., Marcu, K.B., Chieco, P. & Bonafe, M. IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland. The Journal of Clinical Investigation 117, 3988–4002 (2007).PubMedGoogle Scholar
  192. Sastry, K.S., Karpova, Y. & Kulik, G. Epidermal growth factor protects prostate cancer cells from apoptosis by inducing BAD phosphorylation via redundant signaling pathways. The Journal of Biological Chemistry 281, 27367–27377 (2006a).Google Scholar
  193. Sastry, K.S., Smith, A.J., Karpova, Y., Datta, S.R. & Kulik, G. Diverse antiapoptotic signaling pathways activated by vasoactive intestinal polypeptide, epidermal growth factor, and phosphatidylinositol 3-kinase in prostate cancer cells converge on BAD. The Journal of Biological Chemistry 281, 20891–20901 (2006b).Google Scholar
  194. Sato, S., Fujita, N. & Tsuruo, T. Modulation of Akt kinase activity by binding to Hsp90. Proceedings of the National Academy of Sciences of the United States of America 97, 10832–10837 (2000).PubMedGoogle Scholar
  195. Scheufler, C., Brinker, A., Bourenkov, G., Pegoraro, S., Moroder, L., Bartunik, H., Hartl, F.U. & Moarefi, I. Structure of TPR domain-peptide complexes: critical elements in the assembly of the Hsp70-Hsp90 multichaperone machine. Cell 101, 199–210 (2000).PubMedGoogle Scholar
  196. Schuh, S., Yonemoto, W., Brugge, J., Bauer, V.J., Riehl, R.M., Sullivan, W.P. & Toft, D.O. A 90,000-dalton binding protein common to both steroid receptors and the Rous sarcoma virus transforming protein, pp60v-src. The Journal of Biological Chemistry 260, 14292–14296 (1985).PubMedGoogle Scholar
  197. Sciarra, A., Mariotti, G., Gentile, V., Voria, G., Pastore, A., Monti, S. & Di Silverio, F. Neuroendocrine differentiation in human prostate tissue: is it detectable and treatable? BJU International 91, 438–445 (2003).PubMedGoogle Scholar
  198. Segnitz, B. & Gehring, U. The function of steroid hormone receptors is inhibited by the hsp90-specific compound geldanamycin. The Journal of Biological Chemistry 272, 18694–18701 (1997).PubMedGoogle Scholar
  199. Sells, S.F., Wood, D.P., Jr., Joshi-Barve, S.S., Muthukumar, S., Jacob, R.J., Crist, S.A., Humphreys, S. & Rangnekar, V.M. Commonality of the gene programs induced by effectors of apoptosis in androgen-dependent and -independent prostate cells. Cell Growth & Differentation 5, 457–466 (1994).Google Scholar
  200. Sells, S.F., Han, S.S., Muthukkumar, S., Maddiwar, N., Johnstone, R., Boghaert, E., Gillis, D., Liu, G., Nair, P., Monnig, S., Collini, P., Mattson, M.P., Sukhatme, V.P., Zimmer, S.G., Wood, D.P., Jr., McRoberts, J.W., Shi, Y. & Rangnekar, V.M. Expression and function of the leucine zipper protein Par-4 in apoptosis. Molecular and Cellular Biology 17, 3823–3832 (1997).PubMedGoogle Scholar
  201. Shang, Y., Myers, M. & Brown, M. Formation of the androgen receptor transcription complex. Molecular Cell 9, 601–610 (2002).PubMedGoogle Scholar
  202. Sharma, N., Seftor, R.E., Seftor, E.A., Gruman, L.M., Heidger, P.M., Jr., Cohen, M.B., Lubaroff, D.M. & Hendrix, M.J. Prostatic tumor cell plasticity involves cooperative interactions of distinct phenotypic subpopulations: role in vasculogenic mimicry. The Prostate 50, 189–201 (2002).PubMedGoogle Scholar
  203. Sheflin, L., Keegan, B., Zhang, W. & Spaulding, S.W. Inhibiting proteasomes in human HepG2 and LNCaP cells increases endogenous androgen receptor levels. Biochemical and Biophysical Research Communications 276, 144–150 (2000).PubMedGoogle Scholar
  204. Shi, X.B., Ma, A.H., Tepper, C.G., Xia, L., Gregg, J.P., Gandour-Edwards, R., Mack, P.C., Kung, H.J. & deVere White, R.W. Molecular alterations associated with LNCaP cell progression to androgen independence. The Prostate 60, 257–271 (2004).PubMedGoogle Scholar
  205. Signoretti, S., Waltregny, D., Dilks, J., Isaac, B., Lin, D., Garraway, L., Yang, A., Montironi, R., McKeon, F. & Loda, M. p63 is a prostate basal cell marker and is required for prostate development. The American Journal of Pathology 157, 1769–1775 (2000).PubMedGoogle Scholar
  206. Song, C.S., Jung, M.H., Supakar, P.C., Chen, S., Vellanoweth, R.L., Chatterjee, B. & Roy, A.K. Regulation of androgen action by receptor gene inhibition. Annals of the New York Academy of Sciences 761, 97–108 (1995).PubMedGoogle Scholar
  207. St-Arnaud, R., Lachance, R., Kelly, S.J., Belanger, A., Dupont, A. & Labrie, F. Loss of luteinizing hormone bioactivity in patients with prostatic cancer treated with an LHRH agonist and a pure antiandrogen. Clinical Endocrinology 24, 21–30 (1986).PubMedGoogle Scholar
  208. Steck, P.A., Pershouse, M.A., Jasser, S.A., Yung, W.K., Lin, H., Ligon, A.H., Langford, L.A., Baumgard, M.L., Hattier, T., Davis, T., Frye, C., Hu, R., Swedlund, B., Teng, D.H. & Tavtigian, S.V. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nature Genetics 15, 356–362 (1997).PubMedGoogle Scholar
  209. Stefan, M., Claiborn, K.C., Stasiek, E., Chai, J.H., Ohta, T., Longnecker, R., Greally, J.M. & Nicholls, R.D. Genetic mapping of putative Chrna7 and Luzp2 neuronal transcriptional enhancers due to impact of a transgene-insertion and 6.8 Mb deletion in a mouse model of Prader-Willi and Angelman syndromes. BMC Genomics 6, 157 (2005).PubMedGoogle Scholar
  210. Suzuki, A., Matsuzawa, A. & Iguchi, T. Down regulation of Bcl-2 is the first step on Fas-mediated apoptosis of male reproductive tract. Oncogene 13, 31–37 (1996).PubMedGoogle Scholar
  211. Tepper, C.G., Boucher, D.L., Meekay, M.M., Shi, X.B., Li, L.F., Gandour-Edwards, R., Bold, R.J., deVere White, R.W. & Kung, H.J. Androgen withdrawal augments the PI3K-Akt pathway and increases the susceptibility of LNCaP prostate cancer cells to PI3K inhibitors prior to the development of androgen independence. in AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (Miami Beach, FL, 2001).Google Scholar
  212. Tepper, C.G., Boucher, D.L., Ryan, P.E., Ma, A.H., Xia, L., Lee, L.F., Pretlow, T.G. & Kung, H.J. Characterization of a novel androgen receptor mutation in a relapsed CWR22 prostate cancer xenograft and cell line. Cancer Research 62, 6606–6614 (2002).PubMedGoogle Scholar
  213. Tepper, C.G., Vinall, R.L., Wee, C.B., Xue, L., Shi, X.B., Burich, R., Mack, P.C. & de Vere White, R.W. GCP-mediated growth inhibition and apoptosis of prostate cancer cells via androgen receptor-dependent and -independent mechanisms. The Prostate 67, 521–535 (2007).PubMedGoogle Scholar
  214. Teutsch, G., Goubet, F., Battmann, T., Bonfils, A., Bouchoux, F., Cerede, E., Gofflo, D., Gaillard-Kelly, M. & Philibert, D. Non-steroidal antiandrogens: synthesis and biological profile of high-affinity ligands for the androgen receptor. The Journal of Steroid Biochemistry and Molecular Biology 48, 111–119 (1994).PubMedGoogle Scholar
  215. The Gene Ontology Consortium. the gene ontology resource: design and implementation. Genome Research 11, 1425–1433(2001).Google Scholar
  216. The Leuprolide Study Group Leuprolide versus diethylstilbestrol for metastatic prostate cancer. The New England Journal of Medicine 311, 1281–1286 (1984).Google Scholar
  217. Thomas, L.N., Douglas, R.C., Lazier, C.B., Gupta, R., Norman, R.W., Murphy, P.R., Rittmaster, R.S. & Too, C.K. Levels of 5alpha-reductase type 1 and type 2 are increased in localized high grade compared to low grade prostate cancer. The Journal of Urology 179, 147–151 (2008a).Google Scholar
  218. Thomas, L.N., Douglas, R.C., Lazier, C.B., Too, C.K., Rittmaster, R.S. & Tindall, D.J. Type 1 and type 2 5alpha-reductase expression in the development and progression of prostate cancer. European Urology 53, 244–252 (2008b).Google Scholar
  219. Thompson, T.C. & Chung, L.W. Extraction of nuclear androgen receptors by sodium molybdate from normal rat prostates and prostatic tumors. Cancer Research 44, 1019–1026 (1984).PubMedGoogle Scholar
  220. Thompson, V.C., Morris, T.G., Cochrane, D.R., Cavanagh, J., Wafa, L.A., Hamilton, T., Wang, S., Fazli, L., Gleave, M.E. & Nelson, C.C. Relaxin becomes upregulated during prostate cancer progression to androgen independence and is negatively regulated by androgens. The Prostate 66, 1698–1709 (2006).PubMedGoogle Scholar
  221. Tilley, W.D., Marcelli, M. & McPhaul, M.J. Expression of the human androgen receptor gene utilizes a common promoter in diverse human tissues and cell lines. The Journal of Biological Chemistry 265, 13776–13781 (1990).PubMedGoogle Scholar
  222. Tillman, K., Oberfield, J.L., Shen, X.Q., Bubulya, A. & Shemshedini, L. c-Fos dimerization with c-Jun represses c-Jun enhancement of androgen receptor transactivation. Endocrine 9, 193–200 (1998).PubMedGoogle Scholar
  223. Titus, M.A., Schell, M.J., Lih, F.B., Tomer, K.B. & Mohler, J.L. Testosterone and dihydrotestosterone tissue levels in recurrent prostate cancer. Clinical Cancer Research 11, 4653–4657 (2005).PubMedGoogle Scholar
  224. Tolis, G., Ackman, D., Stellos, A., Mehta, A., Labrie, F., Fazekas, A.T., Comaru-Schally, A.M., & Schally, A.V. Tumor growth inhibition in patients with prostatic carcinoma treated with luteinizing hormone-releasing hormone agonists. Proceedings of the National Academy of Sciences of the United States of America 79, 1658–1662 (1982).PubMedGoogle Scholar
  225. Tong, Y., Mentlein, R., Buhl, R., Hugo, H.H., Krause, J., Mehdorn, H.M. & Held-Feindt, J. Overexpression of midkine contributes to anti-apoptotic effects in human meningiomas. Journal of Neurochemistry 100, 1097–1107 (2007).PubMedGoogle Scholar
  226. Trachtenberg, J., Halpern, N. & Pont, A. Ketoconazole: a novel and rapid treatment for advanced prostatic cancer. The Journal of Urology 130, 152–153 (1983).PubMedGoogle Scholar
  227. Trachtenberg, J., Hicks, L.L. & Walsh, P.C. Methods for the determination of androgen receptor content in human prostatic tissue. Investigative Urology 18, 349–354 (1981).PubMedGoogle Scholar
  228. Trachtenberg, J. & Pont, A. Ketoconazole therapy for advanced prostate cancer. Lancet 2, 433–435 (1984).PubMedGoogle Scholar
  229. Tremblay, F. & Marette, A. Amino acid and insulin signaling via the mTOR/p70 S6 kinase pathway. A negative feedback mechanism leading to insulin resistance in skeletal muscle cells. The Journal of Biological Chemistry 276, 38052–38060 (2001).PubMedGoogle Scholar
  230. Trojan, L., Schaaf, A., Steidler, A., Haak, M., Thalmann, G., Knoll, T., Gretz, N., Alken, P. & Michel, M.S. Identification of metastasis-associated genes in prostate cancer by genetic profiling of human prostate cancer cell lines. Anticancer Research 25, 183–191 (2005).PubMedGoogle Scholar
  231. Ueda, K. Detection of the retinoic acid-regulated genes in a RTBM1 neuroblastoma cell line using cDNA microarrayThe Kurume Medical Journal 48, 159–164 (2001).PubMedGoogle Scholar
  232. van Bokhoven, A., Varella-Garcia, M., Korch, C., Johannes, W.U., Smith, E.E., Miller, H.L., Nordeen, S.K., Miller, G.J. & Lucia, M.S. Molecular characterization of human prostate carcinoma cell lines. The Prostate 57, 205–225 (2003).PubMedGoogle Scholar
  233. van Weerden, W.M., van Kreuningen, A., Elissen, N.M., Vermeij, M., de Jong, F.H., van Steenbrugge, G.J. & Schroder, F.H. Castration-induced changes in morphology, androgen levels, and proliferative activity of human prostate cancer tissue grown in athymic nude mice. The Prostate 23, 149–164 (1993).PubMedGoogle Scholar
  234. Vashchenko, N. & Abrahamsson, P.A. Neuroendocrine differentiation in prostate cancer: implications for new treatment modalities. European Urology 47, 147–155 (2005).PubMedGoogle Scholar
  235. Veldscholte, J., Berrevoets, C.A., Brinkmann, A.O., Grootegoed, J.A. & Mulder, E. Anti-androgens and the mutated androgen receptor of LNCaP cells: differential effects on binding affinity, heat-shock protein interaction, and transcription activation. Biochemistry 31, 2393–2399 (1992).PubMedGoogle Scholar
  236. Veldscholte, J., Berrevoets, C.A., Zegers, N.D., van der Kwast, T.H., Grootegoed, J.A. & Mulder, E. Hormone-induced dissociation of the androgen receptor-heat-shock protein complex: use of a new monoclonal antibody to distinguish transformed from nontransformed receptors. Biochemistry 31, 7422–7430 (1992).PubMedGoogle Scholar
  237. Vinall, R.L., Tepper, C.G., Shi, X.B., Xue, L.A., Gandour-Edwards, R. & de Vere White, R.W. The R273H p53 mutation can facilitate the androgen-independent growth of LNCaP by a mechanism that involves H2 relaxin and its cognate receptor LGR7. Oncogene 25, 2082–2093 (2006).PubMedGoogle Scholar
  238. Vinall, R.L., Hwa, K., Ghosh, P., Pan, C.X., Lara, P.N., Jr. & de Vere White, R.W. Combination treatment of prostate cancer cell lines with bioactive soy isoflavones and perifosine causes increased growth arrest and/or apoptosis. Clinical Cancer Research 13, 6204–6216 (2007).PubMedGoogle Scholar
  239. Vlietstra, R.J., van Alewijk, D.C., Hermans, K.G., van Steenbrugge, G.J. & Trapman, J. Frequent inactivation of PTEN in prostate cancer cell lines and xenografts. Cancer Research 58, 2720–2723 (1998).PubMedGoogle Scholar
  240. Wallner, L., Dai, J., Escara-Wilke, J., Zhang, J., Yao, Z., Lu, Y., Trikha, M., Nemeth, J.A., Zaki, M.H. & Keller, E.T. Inhibition of interleukin-6 with CNTO328, an anti-interleukin-6 monoclonal antibody, inhibits conversion of androgen-dependent prostate cancer to an androgen-independent phenotype in orchiectomized mice. Cancer Research 66, 3087–3095 (2006).PubMedGoogle Scholar
  241. Wang, Q., Li, W., Liu, X.S., Carroll, J.S., Janne, O.A., Keeton, E.K., Chinnaiyan, A.M., Pienta, K.J. & Brown, M. A hierarchical network of transcription factors governs androgen receptor-dependent prostate cancer growth. Molecular Cell 27, 380–392 (2007).PubMedGoogle Scholar
  242. Wellington, C.L., Ellerby, L.M., Hackam, A.S., Margolis, R.L., Trifiro, M.A., Singaraja, R., McCutcheon, K., Salvesen, G.S., Propp, S.S., Bromm, M., Rowland, K.J., Zhang, T., Rasper, D., Roy, S., Thornberry, N., Pinsky, L., Kakizuka, A., Ross, C.A., Nicholson, D.W., Bredesen, D.E. & Hayden, M.R. Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract. The Journal of Biological Chemistry 273, 9158–9167 (1998).PubMedGoogle Scholar
  243. Werner, E.D., Lee, J., Hansen, L., Yuan, M. & Shoelson, S.E. Insulin resistance due to phosphorylation of insulin receptor substrate-1 at serine 302. The Journal of Biological Chemistry 279, 35298–35305 (2004).PubMedGoogle Scholar
  244. Westin, P., Bergh, A. & Damber, J.E. Castration rapidly results in a major reduction in epithelial cell numbers in the rat prostate, but not in the highly differentiated Dunning R3327 prostatic adenocarcinoma. The Prostate 22, 65–74 (1993).PubMedGoogle Scholar
  245. Whitesell, L. & Cook, P. Stable and specific binding of heat shock protein 90 by geldanamycin disrupts glucocorticoid receptor function in intact cells. Molecular Endocrinology (Baltimore, Md) 10, 705–712 (1996).Google Scholar
  246. Wissmann, M., Yin, N., Muller, J.M., Greschik, H., Fodor, B.D., Jenuwein, T., Vogler, C., Schneider, R., Gunther, T., Buettner, R., Metzger, E. & Schule, R. Cooperative demethylation by JMJD2C and LSD1 promotes androgen receptor-dependent gene expression. Nature Cell Biology 9, 347–353 (2007).PubMedGoogle Scholar
  247. Wojno, K.J. & Epstein, J.I. The utility of basal cell-specific anti-cytokeratin antibody (34 beta E12) in the diagnosis of prostate cancer. A review of 228 cases. The American Journal of Surgical Pathology 19, 251–260 (1995).PubMedGoogle Scholar
  248. Wolf, D.A., Herzinger, T., Hermeking, H., Blaschke, D. & Horz, W. Transcriptional and posttranscriptional regulation of human androgen receptor expression by androgen. Molecular Endocrinology (Baltimore, Md) 7, 924–936 (1993).Google Scholar
  249. Wright, W.W., Chan, K.C. & Bardin, C.W. Characterization of the stabilizing effect of sodium molybdate on the androgen receptor present in mouse kidney. Endocrinology 108, 2210–2216 (1981).PubMedGoogle Scholar
  250. Wright, M.E., Tsai, M.J. & Aebersold, R. Androgen receptor represses the neuroendocrine transdifferentiation process in prostate cancer cells. Molecular Endocrinology (Baltimore, Md 17, 1726–1737 (2003).Google Scholar
  251. Wu, C. & Huang, J. Phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin pathway is essential for neuroendocrine differentiation of prostate cancer. The Journal of Biological Chemistry 282, 3571–3583 (2007).PubMedGoogle Scholar
  252. Wu, M., Michaud, E.J. & Johnson, D.K. Cloning, functional study and comparative mapping of Luzp2 to mouse chromosome 7 and human chromosome 11p13–11p14. Mammalian Genome 14, 323–334 (2003).PubMedGoogle Scholar
  253. Xu, X.M., Fisher, D.A., Zhou, L., White, F.A., Ng, S., Snider, W.D. & Luo, Y. The transmembrane protein semaphorin 6A repels embryonic sympathetic axons. Journal of Neuroscience 20, 2638–2648 (2000).PubMedGoogle Scholar
  254. Xu, Y., Chen, S.Y., Ross, K.N. & Balk, S.P. Androgens induce prostate cancer cell proliferation through mammalian target of rapamycin activation and post-transcriptional increases in cyclin D proteins. Cancer Research 66, 7783–7792 (2006).PubMedGoogle Scholar
  255. Yamane, K., Toumazou, C., Tsukada, Y., Erdjument-Bromage, H., Tempst, P., Wong, J. & Zhang, Y. JHDM2A, a JmjC-containing H3K9 demethylase, facilitates transcription activation by androgen receptor. Cell 125, 483–495 (2006).PubMedGoogle Scholar
  256. Yang, X., Chen, M.W., Terry, S., Vacherot, F., Chopin, D.K., Bemis, D.L., Kitajewski, J., Benson, M.C., Guo, Y. & Buttyan, R. A human- and male-specific protocadherin that acts through the wnt signaling pathway to induce neuroendocrine transdifferentiation of prostate cancer cells. Cancer Research 65, 5263–5271 (2005).PubMedGoogle Scholar
  257. Yao, J., Liu, Y., Husain, J., Lo, R., Palaparti, A., Henderson, J. & Stifani, S. Combinatorial expression patterns of individual TLE proteins during cell determination and differentiation suggest non-redundant functions for mammalian homologs of Drosophila Groucho. Development Growth and Differentiation 40, 133–146 (1998).Google Scholar
  258. Yao, J., Liu, Y., Lo, R., Tretjakoff, I., Peterson, A. & Stifani, S. Disrupted development of the cerebral hemispheres in transgenic mice expressing the mammalian Groucho homologue transducin-like-enhancer of split 1 in postmitotic neurons. Mechanisms of Development 93, 105–115 (2000).PubMedGoogle Scholar
  259. Yeap, B.B., Krueger, R.G. & Leedman, P.J. Differential posttranscriptional regulation of androgen receptor gene expression by androgen in prostate and breast cancer cells. Endocrinology 140, 3282–3291 (1999).PubMedGoogle Scholar
  260. Yeap, B.B., Voon, D.C., Vivian, J.P., McCulloch, R.K., Thomson, A.M., Giles, K.M., Czyzyk-Krzeska, M.F., Furneaux, H., Wilce, M.C., Wilce, J.A. & Leedman, P.J. Novel binding of HuR and poly(C)-binding protein to a conserved UC-rich motif within the 3′-untranslated region of the androgen receptor messenger RNA. The Journal of Biological Chemistry 277, 27183–27192 (2002).PubMedGoogle Scholar
  261. Yoshimura, T., Kawano, Y., Arimura, N., Kawabata, S., Kikuchi, A. & Kaibuchi, K. GSK-3beta regulates phosphorylation of CRMP-2 and neuronal polarity. Cell 120, 137–149 (2005).PubMedGoogle Scholar
  262. Young, J.C., Obermann, W.M. & Hartl, F.U. Specific binding of tetratricopeptide repeat proteins to the C-terminal 12-kDa domain of hsp90. The Journal of Biological Chemistry 273, 18007–18010 (1998).PubMedGoogle Scholar
  263. Young, J.C., Moarefi, I. & Hartl, F.U. Hsp90: a specialized but essential protein-folding tool. The Journal of Cell Biology 154, 267–273 (2001).PubMedGoogle Scholar
  264. You, Z., Dong, Y., Kong, X., Beckett, L.A., Gandour-Edwards, R. & Melamed, J. Midkine is a NF-kappaB-inducible gene that supports prostate cancer cell survival. BMC Medical Genomics 1, 6 (2008).PubMedGoogle Scholar
  265. Yuan, T.C., Veeramani, S., Lin, F.F., Kondrikou, D., Zelivianski, S., Igawa, T., Karan, D., Batra, S.K. & Lin, M.F. Androgen deprivation induces human prostate epithelial neuroendocrine differentiation of androgen-sensitive LNCaP cells. Endocrine-Related Cancer 13, 151–167 (2006).PubMedGoogle Scholar
  266. Yuan, T.C., Veeramani, S. & Lin, M.F. Neuroendocrine-like prostate cancer cells: neuroendocrine transdifferentiation of prostate adenocarcinoma cells. Endocrine-Related Cancer 14, 531–547 (2007).PubMedGoogle Scholar
  267. Yu, X., Li, P., Roeder, R.G. & Wang, Z. Inhibition of androgen receptor-mediated transcription by amino-terminal enhancer of split. Molecular and Cellular Biology 21, 4614–4625 (2001).PubMedGoogle Scholar
  268. Zelivianski, S., Verni, M., Moore, C., Kondrikov, D., Taylor, R. & Lin, M.F. Multipathways for transdifferentiation of human prostate cancer cells into neuroendocrine-like phenotype. Biochimica et Biophysica Acta 1539, 28–43 (2001).PubMedGoogle Scholar
  269. Zhang, X.Q., Kondrikov, D., Yuan, T.C., Lin, F.F., Hansen, J. & Lin, M.F. Receptor protein tyrosine phosphatase alpha signaling is involved in androgen depletion-induced neuroendocrine differentiation of androgen-sensitive LNCaP human prostate cancer cells. Oncogene 22, 6704–6716 (2003).PubMedGoogle Scholar
  270. Zhang, Y., Akinmade, D. & Hamburger, A.W. The ErbB3 binding protein Ebp1 interacts with Sin3A to repress E2F1 and AR-mediated transcription. Nucleic Acids Research 33, 6024–6033 (2005).PubMedGoogle Scholar
  271. Zhao, G.Q., Bacher, M., Friedrichs, B., Schmidt, W., Rausch, U., Goebel, H.W., Tuohimaa, P. & Aumuller, G. Functional properties of isolated stroma and epithelium from rat ventral prostate during androgen deprivation and estrogen treatment. Experimental and Clinical Endocrinology 101, 69–77 (1993).PubMedGoogle Scholar
  272. Zoubeidi, A., Zardan, A., Beraldi, E., Fazli, L., Sowery, R., Rennie, P., Nelson, C. & Gleave, M. Cooperative interactions between androgen receptor (AR) and heat-shock protein 27 facilitate AR transcriptional activity. Cancer Research 67, 10455–10465 (2007).PubMedGoogle Scholar
  273. Zuber, M.X., Simpson, E.R. & Waterman, M.R. Expression of bovine 17 alpha-hydroxylase cytochrome P-450 cDNA in nonsteroidogenic (COS 1) cells. Science 234, 1258–1261 (1986).PubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.UC Davis Cancer CenterUniversity of California, Davis School of Medicine, UCDMC Research IIISacramentoUSA

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