Transgenic Mouse Models for Prostate Cancer

Identification of an Androgen-Dependent Promoter and Creation and Characterization of the Long Probasin Promoter-Large T Antigen (LPB-Tag) Model
  • Susan Kasper
  • William Tu
  • Richard L. Roberts
  • Scott B. Shappell
Part of the Methods in Molecular Medicine™ book series (MIMM, volume 81)


An appropriate model to study the complex process of prostate tumorigenesis needs to reflect at least some aspects of the human disease presented in the clinic. The progression of prostate cancer includes the development of high-grade prostatic intraepithelial neoplasia (HGPIN, the precursor lesion for usual peripheral zone prostate cancer) (1), invasion, growth and potential dedifferentiation of organ confined tumor (2), extension outside of the prostate (either before or after local therapy), development of metastasis, and the progression from androgen-dependent (AD) to androgen-independent (AI) disease (3). Clinical observations have shown that androgen withdrawal has the greatest impact on the development and progression of prostate cancer. Therefore, androgen deprivation has been the gold standard in treating patients who have advanced prostate cancer (4,5). More than 80% of such patients show a favorable response, as evidenced by a decrease in serum prostate-specific antigen (PSA) levels and tumor regression, but tumor growth could resume despite continuous treatment (6). Although the progressive development of AI is poorly understood, the androgen receptor (AR) appears to be pivotal in the progression from AD to AI prostate cancer. Four possible mechanisms by which the AR may be actively involved in the development of AI include (1) mutations in the AR (5,7, 8, 9, 10, 11); (2) AR amplification (12,13); (3) ligand-independent activation of AR through other signaling pathways (14, 15, 16, 17, 18, 19, 20, 21, 22); and (4) altered activity of AR coregulators (either co-activators or co-inhibitors) (22, 23, 24).


Prostate Cancer Mouse Prostate Prostate Cancer Development tetO Sequence Androgen Receptor Coregulators 
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  1. 1.
    Bostwick, D. G. (1996) Prospective origins of prostate carcinoma. Prostatic intraepithelial neoplasia and atypical adenomatous hyperplasia (review). Cancer 78, 330–336.PubMedCrossRefGoogle Scholar
  2. 2.
    Greene, D. R., Wheeler, T. M., Egawa, S., Dunn, J. K., and Scardino, P. T. (1991) A comparison of the morphological features of cancer arising in the transition zone and in the peripheral zone of the prostate. J. Urol. 146, 1069–1076.PubMedGoogle Scholar
  3. 3.
    Wilding, G. (1992) The importance of steroid hormones in prostate cancer. Cancer Surv. 14, 113–130.PubMedGoogle Scholar
  4. 4.
    Brewster, S. F. and Simons, J. W. (1994) Gene therapy in urological oncology: principles, strategies and potential. Eur. Urol. 25, 177–182.PubMedGoogle Scholar
  5. 5.
    Taplin, M. E., Bubley, G. J., Shuster, T. D., Frantz, M. E., Spooner, A. E., Ogata, G. K., et al. (1995) Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer (see comments). N. Engl. J. Med. 332, 1393–1398.PubMedCrossRefGoogle Scholar
  6. 6.
    Kelly, W. K. and Scher, H. I. (1993) Prostate specific antigen decline after antian-drogen withdrawal: the flutamide withdrawal syndrome. J. Urol. 149, 607–609.PubMedGoogle Scholar
  7. 7.
    Bentel, J. M. and Tilley, W. D. (1996) Androgen receptors in prostate cancer. J. Endocrinol. 151, 1–11.PubMedCrossRefGoogle Scholar
  8. 8.
    Reid, P., Kantoff, P., and Oh, W. (1999) Antiandrogens in prostate cancer. Invest. New Drugs 17, 271–284.PubMedCrossRefGoogle Scholar
  9. 9.
    Buchanan, G., Yang, M., Harris, J. M., Nahm, H. S., Han, G., Moore, N., et al. (2001) Mutations at the boundary of the hinge and ligand binding domain of the androgen receptor confer increased transactivation function. Mol. Endocrinol. 15, 46–56.PubMedCrossRefGoogle Scholar
  10. 10.
    Giovannucci, E., Stampfer, M. J., Krithivas, K., Brown, M., Dahl, D., Brufsky, A., et al. (1997) The CAG repeat within the androgen receptor gene and its relationship to prostate cancer. Proc. Natl. Acad. Sci. USA 94, 3320–3323.PubMedCrossRefGoogle Scholar
  11. 11.
    Irvine, R. A., Yu, M. C., Ross, R. K., and Coetzee, G. A. (1995) The CAG and GGC microsatellites of the androgen receptor gene are in linkage disequilibrium in men with prostate cancer. Cancer Res. 55, 1937–1940.PubMedGoogle Scholar
  12. 12.
    Koivisto, P., Kononen, J., Palmberg, C., Tammela, T., Hyytinen, E., Isola, J., et al. (1997) Androgen receptor gene amplification: A possible molecular mechanism for androgen deprivation therapy failure in prostate cancer. Cancer Res. 57, 314–319.PubMedGoogle Scholar
  13. 13.
    Miyoshi, Y., Uemura, H., Fujinami, K., Mikata, K., Harada, M., Kitamura, H., et al. (2001) Fluorescence in situ hybridization evaluation of c-myc and androgen receptor gene amplification and chromosomal anomalies in prostate cancer in Japanese patients. Prostate 43, 225–232.CrossRefGoogle Scholar
  14. 14.
    Gregory, C. W., Hamil, K. G., Kim, D., Hall, S. H., Pretlow, T. G., Mohler, J. L., et al. (1998) Androgen receptor expression in androgen-independent prostate cancer is associated with increased expression of androgen-regulated genes. Cancer Res. 58, 5718–5724.PubMedGoogle Scholar
  15. 15.
    Chen S-y, Wang, J., Yu G, Liu, W., and Pearce, D. (1997) Androgen and glucocorticoid receptor heterodimer formation. A possible mechanism for mutual inhibition of transcriptional activity. J. Biol. Chem. 272, 14087–14092.PubMedCrossRefGoogle Scholar
  16. 16.
    Ruijter, E., Van De Kaa, C., Miller, G., Ruiter, D., Debruyne, F., and Schalken, J. (1999) Molecular genetics and epidemiology of prostate carcinoma. Endocr. Rev. 20, 22–45.PubMedCrossRefGoogle Scholar
  17. 17.
    Craft, N., Shostak, Y., Carey, M., and Sawyers, C. (1999) A mechanism for hormone-independent prostate cancer through modulation of androgen receptor signaling by the HER-2/neu tyrosine kinase. Nat. Med. 5, 280–285.PubMedCrossRefGoogle Scholar
  18. 18.
    Yeh, S., Lin, H. K., Kang, H. Y., Thin, T. H., Lin, M. F., and Chang, C. (1999) From HER2/Neu signal cascade to androgen receptor and its coactivators: A novel pathway by induction of androgen target genes through MAP kinase in prostate cancer cells. Proc. Natl. Acad. Sci. USA. 96, 5458–5463.PubMedCrossRefGoogle Scholar
  19. 19.
    Wen, Y., Hu, M. C., Makino, K., Spohn, B., Bartholomeusz, G., Yan, D. H., et al. (2000) HER-2/neu promotes androgen-independent survival and growth of prostate cancer cells through the Akt pathway. Cancer Res. 60, 6841–6845.PubMedGoogle Scholar
  20. 20.
    Rajah, R., Valentinis, B., and Cohen, P. (1997) 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. J. Biol. Chem. 272, 12181–12188.PubMedCrossRefGoogle Scholar
  21. 21.
    Hayes S. A., Zarnegar, M., Sharma, M., Yang, F., Peehl, D. M., ten Dijke P., et al. (2001) SMAD3 represses androgen receptor-mediated transcription. Cancer Res. 61, 2112–2118.PubMedGoogle Scholar
  22. 22.
    Kang, H. Y., Lin, H. K., Hu, Y. C., Yeh, S., Huang, K. E., and Chang, C. (2001) From transforming growth factor-beta signaling to androgen action: Identification of Smad3 as an androgen receptor coregulator in prostate cancer cells. Proc. Natl. Acad. Sci. USA. 98, 3018–3023.PubMedCrossRefGoogle Scholar
  23. 23.
    Fujimoto, N., Yeh, S., Kang, H. Y., Inui, S., Chang, H. C., Mizokami, A., et al. (1999) Cloning and characterization of androgen receptor coactivator, ARA55, in human prostate. J. Biol. Chem. 274, 8316–8321.PubMedCrossRefGoogle Scholar
  24. 24.
    Kang, H. Y., Yeh, S., Fujimoto, N., and Chang, C. (1999) Cloning and characterization of human prostate coactivator ARA54, a novel protein that associates with the androgen receptor. J. Biol. Chem. 274, 8570–8576.PubMedCrossRefGoogle Scholar
  25. 25.
    de Pinieux, G., Legrier, M. E., Poirson-Bichat, F., Courty, Y., Bras-Goncalves, R., Dutrillaux, A. M., et al. (2001) Clinical and experimental progression of a new model of human prostate cancer and therapeutic approach. Am. J. Pathol. 159, 753–764.PubMedCrossRefGoogle Scholar
  26. 26.
    Gregory, C. W., Kim, D., Ye, P., D’Ercole, A. J., Pretlow, T. G., Mohler, J. L., et al. (1999) Androgen receptor up-regulates insulin-like growth factor binding protein-5 (IGFBP-5) expression in a human prostate cancer xenograft. Endocrinology 140, 2372–2381.PubMedCrossRefGoogle Scholar
  27. 27.
    Nickerson, T., Chang, F., Lorimer, D., Smeekens, S. P., Sawyers, C. L., and Pol-lak, M. (2001) In vivo progression of lapc-9 and lncap prostate cancer models to androgen independence is associated with increased expression of insulin-like growth factor i (igf-i) and igf-i receptor (igf-ir). Cancer Res. 61, 6276–6280.PubMedGoogle Scholar
  28. 28.
    Zhau, H. E., Li, C. L., and Chung, L. W. (2000) Establishment of human prostate carcinoma skeletal metastasis models. Cancer 88, 2995–3001.PubMedCrossRefGoogle Scholar
  29. 29.
    Korenchuk, S., Lehr, J. E., MClean, L., Lee, Y. G., Whitney, S., Vessella, R., et al. (2001) VCaP, a cell-based model system of human prostate cancer. In Vivo 15, 163–168.PubMedGoogle Scholar
  30. 30.
    Navone, N. M., Logothetis, C. J., von Eschenbach, A. C., and Troncoso, P. (1998) Model systems of prostate cancer: uses and limitations. Cancer Metastasis Rev. 17, 361–371.PubMedCrossRefGoogle Scholar
  31. 31.
    van Weerden, W. M. and Romijn, J.C. (2000) Use of nude mouse xenograft models in prostate cancer research. Prostate 43, 263–271.PubMedCrossRefGoogle Scholar
  32. 32.
    Bostwick, D. G., Ramnani, D., and Qian, J. (2000) Prostatic intraepithelial neoplasia: Animal models 2000. Prostate 43, 286–294.PubMedCrossRefGoogle Scholar
  33. 33.
    Waters, D. J., Bostwick, D. G., and Murphy, G. P. (1998) Conference summary: First International Workshop on Animal models of Prostate Cancer. Prostate 36, 47–48.PubMedCrossRefGoogle Scholar
  34. 34.
    Barrios, R., Lebovitz, R. M., Wiseman, A. L., Weisoly, D. L., Matusik, R. J., DeMayo, F., et al. (1996) RasT24 driven by a probasin promoter induces prostatic hyperplasia in transgenic mice. Transgenics 2, 23–28.Google Scholar
  35. 35.
    Voelkel-Johnson, C., Voeks, D. J., Greenberg, N. M., Barrios, R., Maggouta, F., Kurtz, D. T., et al.(2000) Genomic instability-based transgenic models of prostate cancer. Carcinogenesis 21, 1623–1627.PubMedCrossRefGoogle Scholar
  36. 36.
    Shibata, M. A., Maroulakou, I. G., Jorcyk, C. L., Gold, L. G., Ward, J. M., and Green, J. E. (1996) p53-independent apoptosis during mammary tumor progression in C3(1)/SV40 large T antigen transgenic mice: Auppression of apoptosis during the transition from preneoplasia to carcinoma. Cancer Res. 56, 2998–3003.PubMedGoogle Scholar
  37. 37.
    Kitsberg, D. I. and Leder, P. (1996) Keratinocyte growth factor induces mammary and prostatic hyperplasia and mammary adenocarcinoma in transgenic mice. Oncogene 13, 2507–2515.PubMedGoogle Scholar
  38. 38.
    Hennighausen, L., McKnight, R., Burdon, T., Baik, M., Wall, R. J., and Smith, G. H. (1994) Whey acidic protein extrinsically expressed from the mouse mammary tumor virus long terminal repeat results in hyperplasia of the coagulation gland epithelium and impaired mammary development. Cell Growth Differ. 5, 607–613.PubMedGoogle Scholar
  39. 39.
    DiGiovanni, J., Kiguchi, K., Frijhoff, A., Wilker, E., Bol, D. K., Beltran, L., et al. (2000) Deregulated expression of insulin-like growth factor 1 in prostate epithelium leads to neoplasia in transgenic mice. Proc. Natl. Acad. Sci. USA 97, 3455–3460.PubMedCrossRefGoogle Scholar
  40. 40.
    Greenberg, N. M., DeMayo, F. J., Finegold, M. J., Medina, D., Tilley, W. D., Aspinall, J. O., et al. (1995) Prostate cancer in a transgenic mouse. Proc. Natl. Acad. Sci. USA. 92, 3439–3443.PubMedCrossRefGoogle Scholar
  41. 41.
    Gingrich, J. R., Barrios, R. J., Morton, R. A., Boyce, B. F., DeMayo, F. J., Fine-gold, M. J., et al. (1996) Metastatic prostate cancer in a transgenic mouse. Cancer Res. 56, 4096–4102.PubMedGoogle Scholar
  42. 42.
    Kasper, S., Sheppard, P. C., Yan, Y., Pettigrew, N., Borowsky, A. D., Prins, G. S., et al. (1998) Development, progression and androgen-dependence of prostate tumors in transgenic: A model for prostate cancer. Lab. Invest. 78, 319–334.PubMedGoogle Scholar
  43. 43.
    Masumori, N., Thomas, T. Z., Case, T., Paul, M., Kasper, S., Chaurand, P., et al. (2001) A probasin-large T antigen transgenic mouse line develops prostate adeno and neuroendocrine carcinoma with metastatic potential. Cancer Res. 61, 2239–2249.PubMedGoogle Scholar
  44. 44.
    Tehranian, A., Morris, D. W., Min, B. H., Bird, D. J., Cardiff, R. D., and Barry, P. A. (1996) Neoplastic transformation of prostatic and urogenital epithelium by the polyoma virus middle T gene. Am. J. Pathol. 149, 1177–1191.PubMedGoogle Scholar
  45. 45.
    Garabedian, E. M., Humphrey, P. A., and Gordon, J. I. (1998) A transgenic mouse model of metastatic prostate cancer originating from neuroendocrine cells. Proc. Natl. Acad. Sci. USA. 95, 15382–15387.PubMedCrossRefGoogle Scholar
  46. 46.
    Perez-Stable, C., Altman, N. H., Brown, J., Harbison, M., Cray, C., and Roos, B. A. (1996) Prostate, adrenocortical, and brown adispose tumors in fetal globin T antigen transgenic mice. Lab. Invest. 74, 363–373.PubMedGoogle Scholar
  47. 47.
    Skalnik, D. G., Dorfman, D. M., Williams, D. A., and Orkin, S. H. (1991) Restriction of neuroblastoma to the prostate gland in transgenic mice. Mol. Cell. Biochem. 11, 4518–4527.Google Scholar
  48. 48.
    Pipas, J. M. and Levine, A. J. (2001) Role of T antigen interactions with p53 in tumorigenesis. Semin. Cancer Biol. 11, 23–30.PubMedCrossRefGoogle Scholar
  49. 49.
    Ali, S. H. and Decaprio, J. A. (2001) Cellular transformation by SV40 large T antigen: Interaction with host proteins. Semin. Cancer Biol. 11, 15–23.PubMedCrossRefGoogle Scholar
  50. 50.
    Rundell, K. and Parakati, R. (2001) The role of the SV40 ST antigen in cell growth promotion and transformation. Semin. Cancer Biol. 11, 5–13.PubMedCrossRefGoogle Scholar
  51. 51.
    Myers, R. B., Oelschlager, D., Srivastava, S., and Grizzle, W. E. (1994) Accumulation of the p53 protein occurs more frequently in metastatic than in localized prostatic adenocarcinomas. Prostate 25, 243–248.PubMedCrossRefGoogle Scholar
  52. 52.
    Bookstein, R., Rio, P., Madreperla, S. A., Hong, F., Allred, C., Grizzle, W. E., et al. (1990) Promoter deletion and loss of retinoblastoma gene expression in human prostate carcinoma. Proc. Natl. Acad. Sci. USA. 87, 7762–7766.PubMedCrossRefGoogle Scholar
  53. 53.
    Bookstein, R., Shew, J. Y., Chen, P. L., Scully, P., and Lee, W. H. (1990) Suppression of tumorigenicity of human prostate carcinoma cells by replacing a mutated RB gene. Science 247, 712–715.PubMedCrossRefGoogle Scholar
  54. 54.
    Bookstein, R., MacGrogan, D., Hilsenbeck, S. G., Sharkey, F., and Allred, D. C. (1993) p53 is mutated in a subset of advanced-stage prostate cancers. Cancer Res. 53, 3369–3373.PubMedGoogle Scholar
  55. 55.
    Jasani, B., Cristaudo, A., Emri, S. A., Gazdar, A. F., Gibbs, A., Krynska, B., et al. (2001) Association of SV40 with human tumours. Semin. Cancer Biol. 11, 49–61.PubMedCrossRefGoogle Scholar
  56. 56.
    Shibata, M. A., Ward, J. M., Devor, D. E., Liu, M. L., and Green, J. E. (1996) Progression of prostatic intraepithelial neoplasia to invasive carcinoma in C3(1)/SV40 large T antigen transgenic mice: Histopathological and molecular biological alterations. Cancer Res. 56, 4894–4903.PubMedGoogle Scholar
  57. 57.
    Huss, W. J., Hanrahan, C. F., Barrios, R. J., Simons, J. W., and Greenberg, N. M. (2001) Angiogenesis and prostate cancer: identification of a molecular progression switch. Cancer Res. 61, 2736–2743.PubMedGoogle Scholar
  58. 58.
    Charest, N. J., Zhou, Z. X., Lubahn, D. B., Olsen, K. L., Wilson, E. M., and French, F. S. (1991) A frameshift mutation destabilizes androgen receptor messenger RNA in the Tfm mouse. Mol. Endocrinol. 5, 573–581.PubMedCrossRefGoogle Scholar
  59. 59.
    He, W. W., Kumar, M. V., and Tindall, D. J.(1991) A frame-shift mutation in the androgen receptor gene causes complete androgen insensitivity in the testicular-feminized mouse. Nucleic Acids Res. 19, 2373–2378.PubMedCrossRefGoogle Scholar
  60. 60.
    Cunha, G. R. and Lung, B. (1978) The possible influence of temporal factors in androgenic responsiveness of urogenital tissue recombinants from wild-type and androgen-insensitive (Tfm) mice. J. Exp. Zool. 205, 181–193.PubMedCrossRefGoogle Scholar
  61. 61.
    Cunha, G. R. and Chung, L. W. (1981) Stromal-epithelial interactions—I. Induction of prostatic phenotype in urothelium of testicular feminized (Tfm/y) mice. J. Steroid Biochem. 14, 1317–1324.PubMedCrossRefGoogle Scholar
  62. 62.
    Zheng, B., Mills, A. A., and Bradley, A. (1999) A system for rapid generation of coat color-tagged knockouts and defined chromosomal rearrangements in mice. Nucleic Acids Res. 27, 2354–2360.PubMedCrossRefGoogle Scholar
  63. 63.
    Hertzog, P. J. and Kola, I. (2001) Overview. Gene knockouts. Methods Mol. Biol. 158, 1–10.PubMedGoogle Scholar
  64. 64.
    Eddy, E. M., Washburn, T. F., Bunch, D. O., Goulding, E. H., Gladen, B. C., Lubahn, D. B., et al. (1996) Targeted disruption of the estrogen receptor gene in male mice causes alteration of spermatogenesis and infertility. Endocrinology 137, 4796–4805.PubMedCrossRefGoogle Scholar
  65. 65.
    Risbridger, G. P., Wang, H., Frydenberg, M., and Cunha, G. (2001) The metaplastic effects of estrogen on mouse prostate epithelium: Proliferation of cells with basal cell phenotype. Endocrinology 142, 2443–2450.PubMedCrossRefGoogle Scholar
  66. 66.
    Colombel, M., Radvanyi, F., Blanche, M., Abbou, C., Buttyan, R., Donehower, L. A., et al. (1995) Androgen suppressed apoptosis is modified in p53 deficient mice. Oncogene 10, 1269–1274.PubMedGoogle Scholar
  67. 67.
    Di Cristofano, A., De Acetis, M., Koff, A., Cordon-Cardo, C., and Pandolfi, P. P. (1998) Pten and p27KIP1 cooperate in prostate cancer tumor suppression in the mouse. Nat. Genet. 27, 134–135.Google Scholar
  68. 68.
    Luo, J. L., Yang, Q., Tong, W. M., Hergenhahn, M., Wang, Z. Q., and Hollstein, M. (2001) Knock-in mice with a chimeric human/murine p53 gene develop normally and show wild-type p53 responses to DNA damaging agents: a new biomedical research tool. Oncogene 20, 320–328.PubMedCrossRefGoogle Scholar
  69. 69.
    Wang, Y., Hayward, S. W., Donjacour, A. A., Young, P., Jacks, T., Sage, J., et al. (2000) Sex hormone-induced carcinogenesis in Rb-deficient prostate tissue. Cancer Res. 60, 6008–6017.PubMedGoogle Scholar
  70. 70.
    Sauer, B. (1998) Inducible gene targeting in mice using the Cre/lox system. Methods 14, 381–392.PubMedCrossRefGoogle Scholar
  71. 71.
    Wu, X., Wu, J., Huang, J., Powell, W. C., Zhang, J., Matusik, R. J., et al. (2001) Generation of a prostate epithelial cell-specific Cre transgenic mouse model for tissue-specific gene ablation. Mech. Dev. 101, 61–69.PubMedCrossRefGoogle Scholar
  72. 72.
    Sauer, B. (1992) Identification of cryptic lox sites in the yeast genome by selection for Cre-mediated chromosome translocations that confer multiple drug resistance. J. Mol. Biol. 223, 911–928.PubMedCrossRefGoogle Scholar
  73. 73.
    Lottmann, H., Vanselow, J., Hessabi, B., and Walther, R. (2001) The Tet-On system in transgenic mice: Inhibition of the mouse pdx-1 gene activity by antisense RNA expression in pancreatic beta-cells. J. Mol. Med. 79, 321–328.PubMedCrossRefGoogle Scholar
  74. 74.
    Zhu, Z., Ma, B., Homer, R. J., Zheng, T., and Elias, J. A. (2001) Use of the tetra-cycline-controlled transcriptional silencer (tTS) to eliminate transgene leak in inducible overexpression transgenic mice. J. Biol. Chem. 276, 25222–25229.PubMedCrossRefGoogle Scholar
  75. 75.
    Freundlieb, S., Schirra-Muller, C., and Bujard, H. (1999) A tetracycline controlled activation/repression system with increased potential for gene transfer into mammalian cells. J. Gene Med. 1, 4–12.PubMedCrossRefGoogle Scholar
  76. 76.
    Wakita, K., McCormick, F., and Tetsu, O. (2001) Method for screening ecdysone-inducible stable cell lines. Biotechniques 31, 414–418.PubMedGoogle Scholar
  77. 77.
    Saez, E., Nelson, M. C., Eshelman, B., Banayo, E., Koder, A., Cho, G. J., et al. (2000) Identification of ligands and coligands for the ecdysone-regulated gene switch. Proc. Natl. Acad. Sci. USA 97, 14512–14517.PubMedCrossRefGoogle Scholar
  78. 78.
    Constantino, S., Santos, R., Gisselbrecht, S., and Gouilleux, F. (2001) The ecdysone inducible gene expression system: unexpected effects of muristerone A and ponasterone A on cytokine signaling in mammalian cells. Eur. Cytokine. Netw. 12, 365–367.PubMedGoogle Scholar
  79. 79.
    Lee, C., Sensibar, J. A., Dudek, S. M., Hiipakka, R. A., and Liao, S. T. (1990) Prostatic ductal system in rats: regional variation in morphological and functional activities. Biol. Reprod. 43, 1079–1086.PubMedCrossRefGoogle Scholar
  80. 80.
    Price, D. (1963) Comparative aspects of development and structure in the prostate, in Biology of the Prostate and Related Tissues (Vollmer, E. P. and Kauff-mann, G., eds.) US Government Printing Office, Washington, D.C., pp. 1–28.Google Scholar
  81. 81.
    Spence, A. M., Sheppard, P. C., Davie, J. R., Matuo, Y., Nishi, N., McKeehan, W. L., et al. (1989) Regulation of a bifunctional mRNA results in synthesis of secreted and nuclear probasin. Proc. Natl. Acad. Sci. USA. 86, 7843–7847.PubMedCrossRefGoogle Scholar
  82. 82.
    Spence, A. M., Sheppard, P. C., Davie, J. R., Matuo, Y., Nishi, N., McKeehan, W. L., et al. (1989) Regulation of a bifunctional mRNA results in synthesis of secreted and nuclear probasin. Proc. Natl. Acad. Sci. USA 86, 7843–7847.PubMedCrossRefGoogle Scholar
  83. 83.
    Matuo, Y., Nishi, N., Muguruma, Y., Yoshitake, Y., Kurata, N., and Wada, F. (1985) Localization of prostatic basic protein (“probasin”) in the rat prostates by use of monoclonal antibody. Biochem. Biophys. Res. Commun. 130, 293–300.PubMedCrossRefGoogle Scholar
  84. 84.
    Dodd, J. G., Sheppard, P. C., and Matusik, R. J. (1983) Characterization and cloning of rat dorsal prostate mRNAs. Androgen regulation of two closely related abundant mRNAs. J. Biol. Chem. 258, 10731–10737.PubMedGoogle Scholar
  85. 85.
    Rennie, P. S., Bruchovsky, N., Leco, K. J., Sheppard, P. C., McQueen, S. A., Cheng, H., et al. (1993) Characterization of two cis-acting elements involved in the androgen regulation of the probasin gene. Mol. Endocrinol. 7, 23–36.PubMedCrossRefGoogle Scholar
  86. 86.
    Greenberg, N. M., DeMayo, F. J., Sheppard, P. C., Barrios, R., Lebovitz, M., Finegold, M., et al. (1994) The rat probasin gene promoter directs hormonally and developmentally regulated expression of a heterologous gene specifically to the prostate in transgenic mice. Mol. Endocrinol. 8, 230–239.PubMedCrossRefGoogle Scholar
  87. 87.
    Matusik, R. J., Kreis, C., McNicol, P., Sweetland, R., Mullin, C., Fleming, W. H., et al. (1986) Regulation of prostatic genes: role of androgens and zinc in gene expression. Biochem. Cell Biol. 64, 601–607.PubMedCrossRefGoogle Scholar
  88. 88.
    Nachtigal, M. W., Nickel, B. E., Klassen, M. E., Zhang, W., Eberhardt, N. L., and Cattini, P. A. (1989) Human chorionic somatommammotropin and growth hormone gene expression in rat pituitary tumour cells is dependent on proximal promoter sequences. Nucleic Acids Res. 17, 4327–4337.PubMedCrossRefGoogle Scholar
  89. 89.
    Zhang, J., Thomas, T. Z., Kasper, S., and Matusik, R. J. (2000) A small composite probasin promoter confers high levels of prostate-specific gene expression through regulation by androgens and glucocorticoids in vitro and in vivo. Endocrinology 141, 4698–4710.PubMedCrossRefGoogle Scholar
  90. 90.
    Cleutjens, K. B., van der Korput, H. A., Ehren-van Eekelen, C. C., Sikes, R. A., Fasciana, C., Chung, L. W., et al. (1997) A 6-kb promoter fragment mimics in transgenic mice the prostate-specific and androgen-regulated expression of the endogenous prostate-specific antigen gene in humans. Mol. Endocrinol. 11, 1256–1265.PubMedCrossRefGoogle Scholar
  91. 91.
    Daelemans, D., De Clercq, E., and Vandamme, A. (2001) A quantitative GFP-based bioassay for the detection of HIV-1 Tat transactivation inhibitors. J. Virol. Methods 96, 183–188.PubMedCrossRefGoogle Scholar
  92. 92.
    Veldscholte, J., Berrevoets, C. A., Ris-Stalpers, C., Kuiper, G. G., Jenster, G., Trapman, J., et al. (1992) The androgen receptor in LNCaP cells contains a mutation in the ligand binding domain which affects steroid binding characteristics and response to antiandrogens. J. Steroid Biochem. Mol. Biol. 41, 665–669.PubMedCrossRefGoogle Scholar
  93. 93.
    Liu, N., Gao, F., Han, Z., Xu, X., Underhill, C. B., and Zhang, L. (2001) Hyaluronan synthase 3 overexpression promotes the growth of TSU prostate cancer cells. Cancer Res. 61, 5207–5214.PubMedGoogle Scholar
  94. 94.
    Kasper, S., Rennie, P. S., Bruchovsky, N., Sheppard, P. C., Cheng, H., Lin, L., et al. (1994) Cooperative binding of androgen receptors to two DNA sequences is required for androgen induction of the probasin gene. J. Biol. Chem. 269, 31763–31769.PubMedGoogle Scholar
  95. 95.
    Kasper, S., Rennie, P. S., Bruchovsky, N., Lin, L., Cheng, H., Snoek, R., et al. (1999) Selective activation of the probasin androgen responsive region by steroid hormones. J. Mol. Endocrinol. 22, 313–325.PubMedCrossRefGoogle Scholar
  96. 96.
    Brookes, D. E., Zandvliet, D., Watt, F., Russell, P. J., and Molloy, P. L. (1998) Relative activity and specificity of promoters from prostate-expressed genes. Prostate 35, 18–26.PubMedCrossRefGoogle Scholar
  97. 97.
    Yan, Y., Sheppard, P. C., Kasper, S., Lin, L., Hoare, S., Kapoor, A., et al. (1997) A large fragment of the probasin promoter targets high levels of transgene expression to the prostate of transgenic mice. Prostate 32, 129–139.PubMedCrossRefGoogle Scholar
  98. 98.
    Sleigh, M. J., Topp, W. C., Hanich, R., and Sambrook, J. F. (1978) Mutants of SV40 with an altered small t protein are reduced in their ability to transform cells. Cell 14, 79–88.PubMedCrossRefGoogle Scholar
  99. 99.
    Hogan, B., Beddington, R., Costantini, F., and Lacy, E. (eds.) (2001) Manipulating the Mouse Embryo, A Laboratory Manual, 2nd edition. Cold Springs Harbor Press.Google Scholar
  100. 100.
    Hayward, S. W., Brody, J. R., and Cunha, G. R. (1996) An edgewise look at basal epithelial cells: three-dimensional views of the rat prostate, mammary gland and salivary gland. Differentiation 60, 219–227.PubMedCrossRefGoogle Scholar
  101. 101.
    Bonkhoff, H. and Remberger, K. (1998) Morphogenetic concepts of normal and abnormal growth in the human prostate. Virchows Arch. 433, 195–202.PubMedCrossRefGoogle Scholar
  102. 102.
    Cox, M. E., Deeble, P. D., Bissonette, E. A., and Parsons, S. J. (2000) Activated 3′,5′-cyclic AMP-dependent protein kinase is sufficient to induce neuroendocrine-like differentiation of the LNCaP prostate tumor cell line. J. Biol. Chem. 275, 13812–13818.PubMedCrossRefGoogle Scholar
  103. 103.
    Zelivianski, S., Verni, M., Moore, C., Kondrikov, D., Taylor, R., and Lin, M. F. (2001) Multipathways for transdifferentiation of human prostate cancer cells into neuroendocrine-like phenotype. Biochim. Biophys. Acta 1539, 28–43.PubMedCrossRefGoogle Scholar
  104. 104.
    Gingrich, J. R., Barrios, R. J., Foster, B. A., and Greenberg, M. N. (1999) Pathologic progression of autochthonous prostate cancer in the TRAMP model. Prostate Cancer Prostatic Dis. 6, 1–6.Google Scholar
  105. 105.
    Chaurand, P., DaGue, B. B., Ma, S., Kasper, S., and Caprioli, R. M. (2001) Strainbased sequence variations and structure analysis of murine prostate specific spermine binding protein using mass spectrometry. Biochemistry 40, 9725–9733.PubMedCrossRefGoogle Scholar
  106. 106.
    Zhang Z. F., Thomas, T. Z., Kasper, S., and Matusik, R. J. (2000) A small composite probasin promoter confers high levels of prostate-specific gene expression through regulation by androgens and glucocorticoid in vitro and in vivo. Endocrinology 141, 4698–4710.PubMedCrossRefGoogle Scholar
  107. 107.
    Andriani, F., Nan, B., Yu, J., Li, X., Weigel, N. L., McPhaul, et al. (2001) Use of the probasin promoter arr(2)pb to express bax in androgen receptor-positive prostate cancer cells. J. Natl. Cancer Inst. 93, 1314–1324.PubMedCrossRefGoogle Scholar
  108. 108.
    Chaurand, P., Stoeckli, M., and Caprioli, R. M. (1999) Direct profiling of proteins in biological tissue sections by MALDI mass spectrometry. Anal. Chem. 71, 5263–5270.PubMedCrossRefGoogle Scholar
  109. 109.
    Hamer, D.H. and Walling, M. (1982) Regulation in vivo of a cloned mammalian gene: cadmium induces the transcription of a mouse metallothionein gene in SV40 vectors. J. Mol. Appl. Genet. 1, 273–288.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2003

Authors and Affiliations

  • Susan Kasper
    • 1
  • William Tu
    • 1
    • 2
  • Richard L. Roberts
    • 3
  • Scott B. Shappell
    • 4
  1. 1.Department of Urologic SurgeryVanderbilt University Medical CenterNashville
  2. 2.Department of Cancer BiologyVanderbilt University Medical CenterNashville
  3. 3.Department of Pathology and The Vanderbilt Prostate Cancer CenterVanderbilt University Medical CenterNashville
  4. 4.The Vanderbilt Prostate Cancer Center, Departments of Urologic Surgery and Pathology, Vanderbilt Ingram Cancer CenterVanderbilt University Medical CenterNashville

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