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Increased Expression of Genes Converting Adrenal Androgens to Testosterone in Castration-Recurrent Prostate Cancer

  • Steven P. Balk
Chapter

Abstract

Androgen deprivation is still the standard systemic therapy for locally advanced or metastatic prostate cancer (PCa), but patients invariably relapse with a more aggressive form of PCa that has been termed castration-recurrent PCa (CRPCa). The androgen receptor (AR) is expressed at high levels in most cases of CRPCa, and these tumors resume their expression of multiple AR regulated genes, which indicates that AR transcriptional activity becomes reactivated at this stage of the disease. Mechanisms that may contribute to AR reactivation in CRPCa include increased AR protein expression, AR mutations, increased expression of transcriptional coactivator proteins, and activation of signal transduction pathways that can enhance AR responses to low levels of androgens. Recent data indicate that a further mechanism for AR reactivation in CRPCa cells may be through increased intracellular synthesis of testosterone and 5α-dihydrotestosterone (DHT). The enzymes that mediate androgen synthesis and metabolism in normal prostate and in PCa, and evidence indicating that their increased expression contributes to the development of CRPCa, are outlined in this chapter. The early use of therapies that more aggressively block androgen production may enhance responses to androgen deprivation therapy, and prevent or delay the adaptations that eventually lead to CRPCa.

Keywords

Androgen Receptor LNCaP Cell Normal Prostate Androgen Synthesis Androgen Receptor Antagonist 
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. Andersson, S., Geissler, W.M., Patel, S., and Wu, L.(1995). The molecular biology of androgenic 17 beta-hydroxysteroid dehydrogenases. J. Steroid Biochem. Mol. Biol.53, 37–39.PubMedCrossRefGoogle Scholar
  2. Baek, S.H., Ohgi, K.A., Nelson, C.A., Welsbie, D., Chen, C., Sawyers, C.L., Rose, D.W., and Rosenfeld, M.G.(2006). Ligand-specific allosteric regulation of coactivator functions of androgen receptor in prostate cancer cells. Proc. Natl. Acad. Sci. U. S. A103, 3100–3105.PubMedCrossRefGoogle Scholar
  3. Bauman, D.R., Steckelbroeck, S., Peehl, D.M., and Penning, T.M.(2006a). Transcript profiling of the androgen signal in normal prostate, benign prostatic hyperplasia, and prostate cancer. Endocrinology147, 5806–5816.CrossRefGoogle Scholar
  4. Bauman, D.R., Steckelbroeck, S., Williams, M.V., Peehl, D.M., and Penning, T.M.(2006b). Identification of the major oxidative 3alpha-hydroxysteroid dehydrogenase in human prostate that converts 5alpha-androstane-3alpha,17beta-diol to 5alpha-dihydrotestosterone: a potential therapeutic target for androgen-dependent disease. Mol. Endocrinol.20, 444–458.CrossRefGoogle Scholar
  5. Belanger, A., Pelletier, G., Labrie, F., Barbier, O., and Chouinard, S.(2003). Inactivation of androgens by UDP-glucuronosyltransferase enzymes in humans. Trends Endocrinol. Metab.14, 473–479.PubMedCrossRefGoogle Scholar
  6. Belanger, B., Belanger, A., Labrie, F., Dupont, A., Cusan, L., and Monfette, G.(1989). Comparison of residual C-19 steroids in plasma and prostatic tissue of human, rat and guinea pig after castration: unique importance of extratesticular androgens in men. J. Steroid Biochem.32, 695–698.PubMedCrossRefGoogle Scholar
  7. Bjelfman, C., Soderstrom, T.G., Brekkan, E., Norlen, B.J., Egevad, L., Unge, T., Andersson, S., and Rane, A.(1997). Differential gene expression of steroid 5 alpha-reductase 2 in core needle biopsies from malignant and benign prostatic tissue. J. Clin. Endocrinol. Metab82, 2210–2214.PubMedCrossRefGoogle Scholar
  8. Bonkhoff, H., Stein, U., Aumuller, G., and Remberger, K.(1996). Differential expression of 5 alpha-reductase isoenzymes in the human prostate and prostatic carcinomas. Prostate29, 261–267.PubMedCrossRefGoogle Scholar
  9. Chen, C.D., Welsbie, D.S., Tran, C., Baek, S.H., Chen, R., Vessella, R., Rosenfeld, M.G., and Sawyers, C.L.(2004). Molecular determinants of resistance to antiandrogen therapy. Nat. Med.10, 33–39.PubMedCrossRefGoogle Scholar
  10. Cheng, S., Brzostek, S., Lee, S.R., Hollenberg, A.N., and Balk, S.P.(2002). Inhibition of the dihydrotestosterone-activated androgen receptor by nuclear receptor corepressor. Mol. Endocrinol.16, 1492–1501.PubMedCrossRefGoogle Scholar
  11. Chouinard, S., Pelletier, G., Belanger, A., and Barbier, O.(2004). Cellular specific expression of the androgen-conjugating enzymes UGT2B15 and UGT2B17 in the human prostate epithelium. Endocr. Res.30, 717–725.PubMedCrossRefGoogle Scholar
  12. Chouinard, S., Pelletier, G., Belanger, A., and Barbier, O.(2006). Isoform-specific regulation of uridine diphosphate-glucuronosyltransferase 2B enzymes in the human prostate: differential consequences for androgen and bioactive lipid inactivation. Endocrinology147, 5431–5442.PubMedCrossRefGoogle Scholar
  13. Desmond, J.C., Mountford, J.C., Drayson, M.T., Walker, E.A., Hewison, M., Ride, J.P., Luong, Q.T., Hayden, R.E., Vanin, E.F., and Bunce, C.M.(2003). The aldo-keto reductase AKR1C3 is a novel suppressor of cell differentiation that provides a plausible target for the non-cyclooxygenase-dependent antineoplastic actions of nonsteroidal anti-inflammatory drugs. Cancer Res.63, 505–512.PubMedGoogle Scholar
  14. Dufort, I., Rheault, P., Huang, X.F., Soucy, P., and Luu-The, V.(1999). Characteristics of a highly labile human type 5 17beta-hydroxysteroid dehydrogenase. Endocrinology140, 568–574.PubMedCrossRefGoogle Scholar
  15. El Alfy, M., Luu-The, V., Huang, X.F., Berger, L., Labrie, F., and Pelletier, G.(1999). Localization of type 5 17beta-hydroxysteroid dehydrogenase, 3beta-hydroxysteroid dehydrogenase, and androgen receptor in the human prostate by in situ hybridization and immunocytochemistry. Endocrinology140, 1481–1491.PubMedCrossRefGoogle Scholar
  16. Elo, J.P., Akinola, L.A., Poutanen, M., Vihko, P., Kyllonen, A.P., Lukkarinen, O., and Vihko, R.(1996). Characterization of 17beta-hydroxysteroid dehydrogenase isoenzyme expression in benign and malignant human prostate. Int. J. Cancer66, 37–41.PubMedCrossRefGoogle Scholar
  17. Ettinger, S.L., Sobel, R., Whitmore, T.G., Akbari, M., Bradley, D.R., Gleave, M.E., and Nelson, C.C.(2004). Dysregulation of sterol response element-binding proteins and downstream effectors in prostate cancer during progression to androgen independence. Cancer Res.64, 2212–2221.PubMedCrossRefGoogle Scholar
  18. Fowler, J.E., Jr., Pandey, P., Seaver, L.E., and Feliz, T.P.(1995). Prostate specific antigen after gonadal androgen withdrawal and deferred flutamide treatment. J. Urol.154, 448–453.PubMedCrossRefGoogle Scholar
  19. Fromont, G., Chene, L., Vidaud, M., Vallancien, G., Mangin, P., Fournier, G., Validire, P., Latil, A., and Cussenot, O.(2005). Differential expression of 37 selected genes in hormone-refractory prostate cancer using quantitative taqman real-time RT-PCR. Int. J. Cancer114, 174–181.PubMedCrossRefGoogle Scholar
  20. Fung, K.M., Samara, E.N., Wong, C., Metwalli, A., Krlin, R., Bane, B., Liu, C.Z., Yang, J.T., Pitha, J.V., Culkin, D.J., Kropp, B.P., Penning, T.M., and Lin, H.K.(2006). Increased expression of type 2 3alpha-hydroxysteroid dehydrogenase/type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3) and its relationship with androgen receptor in prostate carcinoma. Endocr. Relat. Cancer13, 169–180.PubMedCrossRefGoogle Scholar
  21. Geller, J.(1985). Rationale for blockade of adrenal as well as testicular androgens in the treatment of advanced prostate cancer. Semin. Oncol.12, 28–35.PubMedGoogle Scholar
  22. Geller, J. and Albert, J.(1987). Effects of castration compared with total androgen blockade on tissue dihydrotestosterone (DHT) concentration in benign prostatic hyperplasia (BPH). Urol. Res.15, 151–153.PubMedCrossRefGoogle Scholar
  23. Geller, J., Albert, J.D., Nachtsheim, D.A., and Loza, D.(1984). Comparison of prostatic cancer tissue dihydrotestosterone levels at the time of relapse following orchiectomy or estrogen therapy. J. Urol.132, 693–696.PubMedGoogle Scholar
  24. Gingras, S. and Simard, J.(1999). Induction of 3beta-hydroxysteroid dehydrogenase/isomerase type 1 expression by interleukin-4 in human normal prostate epithelial cells, immortalized keratinocytes, colon, and cervix cancer cell lines. Endocrinology140, 4573–4584.PubMedCrossRefGoogle Scholar
  25. Guillemette, C., Hum, D.W., and Belanger, A.(1996). Regulation of steroid glucuronosyltransferase activities and transcripts by androgen in the human prostatic cancer LNCaP cell line. Endocrinology137, 2872–2879.PubMedCrossRefGoogle Scholar
  26. Harkonen, P., Torn, S., Kurkela, R., Porvari, K., Pulkka, A., Lindfors, A., Isomaa, V., and Vihko, P.(2003). Sex hormone metabolism in prostate cancer cells during transition to an androgen-independent state. J. Clin. Endocrinol. Metab.88, 705–712.PubMedCrossRefGoogle Scholar
  27. Harrington, W.R., Sengupta, S., and Katzenellenbogen, B.S.(2006). Estrogen regulation of the glucuronidation enzyme UGT2B15 in estrogen receptor-positive breast cancer cells. Endocrinology147, 3843–3850.PubMedCrossRefGoogle Scholar
  28. Heemers, H., Maes, B., Foufelle, F., Heyns, W., Verhoeven, G., and Swinnen, J.V.(2001). Androgens stimulate lipogenic gene expression in prostate cancer cells by activation of the sterol regulatory element-binding protein cleavage activating protein/sterol regulatory element-binding protein pathway. Mol. Endocrinol.15, 1817–1828.PubMedCrossRefGoogle Scholar
  29. Hodgson, M.C., Astapova, I., Hollenberg, A.N., and Balk, S.P.(2007). Activity of androgen receptor antagonist bicalutamide in prostate cancer cells is independent of NCoR and SMRT corepressors. Cancer Res.67, 8388–8395.PubMedCrossRefGoogle Scholar
  30. Holzbeierlein, J., Lal, P., LaTulippe, E., Smith, A., Satagopan, J., Zhang, L., Ryan, C., Smith, S., Scher, H., Scardino, P., Reuter, V., and Gerald, W.L.(2004). Gene expression analysis of human prostate carcinoma during hormonal therapy identifies androgen-responsive genes and mechanisms of therapy resistance. Am. J. Pathol.164, 217–227.PubMedCrossRefGoogle Scholar
  31. Iehle, C., Radvanyi, F., Gil Diez de, M., Ouafik, L.H., Gerard, H., Chopin, D., Raynaud, J.P., and Martin, P.M.(1999). Differences in steroid 5alpha-reductase iso-enzymes expression between normal and pathological human prostate tissue. J. Steroid Biochem. Mol. Biol.68, 189–195.PubMedCrossRefGoogle Scholar
  32. Ji, Q., Chang, L., Stanczyk, F.Z., Ookhtens, M., Sherrod, A., and Stolz, A.(2007). Impaired dihydrotestosterone catabolism in human prostate cancer: critical role of AKR1C2 as a pre-receptor regulator of androgen receptor signaling. Cancer Res.67, 1361–1369.PubMedCrossRefGoogle Scholar
  33. Ji, Q., Chang, L., VanDenBerg, D., Stanczyk, F.Z., and Stolz, A.(2003). Selective reduction of AKR1C2 in prostate cancer and its role in DHT metabolism. Prostate54, 275–289.PubMedCrossRefGoogle Scholar
  34. Joyce, R., Fenton, M.A., Rode, P., Constantine, M., Gaynes, L., Kolvenbag, G., DeWolf, W., Balk, S., Taplin, M.E., and Bubley, G.J.(1998). High dose bicalutamide for androgen independent prostate cancer: effect of prior hormonal therapy. J. Urol.159, 149–153.PubMedCrossRefGoogle Scholar
  35. Komoto, J., Yamada, T., Watanabe, K., and Takusagawa, F.(2004). Crystal structure of human prostaglandin F synthase (AKR1C3). Biochemistry43, 2188–2198.PubMedCrossRefGoogle Scholar
  36. Krieg, M., Bartsch, W., Janssen, W., and Voigt, K.D.(1979). A comparative study of binding, metabolism and endogenous levels of androgens in normal, hyperplastic and carcinomatous human prostate. J. Steroid Biochem.11, 615–624.PubMedCrossRefGoogle Scholar
  37. Labrie, F., Luu-The, V., Lin, S.X., Simard, J., and Labrie, C.(2000). Role of 17 beta-hydroxysteroid dehydrogenases in sex steroid formation in peripheral intracrine tissues. Trends Endocrinol. Metab.11, 421–427.PubMedCrossRefGoogle Scholar
  38. Lin, H.K., Jez, J.M., Schlegel, B.P., Peehl, D.M., Pachter, J.A., and Penning, T.M.(1997). Expression and characterization of recombinant type 2 3 alpha-hydroxysteroid dehydrogenase (HSD) from human prostate: demonstration of bifunctional 3 alpha/17 beta-HSD activity and cellular distribution. Mol. Endocrinol.11, 1971–1984.PubMedCrossRefGoogle Scholar
  39. Lin, H.K., Steckelbroeck, S., Fung, K.M., Jones, A.N., and Penning, T.M.(2004). Characterization of a monoclonal antibody for human aldo-keto reductase AKR1C3 (type 2 3alpha-hydroxysteroid dehydrogenase/type 5 17beta-hydroxysteroid dehydrogenase); immunohistochemical detection in breast and prostate. Steroids69, 795–801.PubMedCrossRefGoogle Scholar
  40. Luo, J., Dunn, T.A., Ewing, C.M., Walsh, P.C., and Isaacs, W.B.(2003). Decreased gene expression of steroid 5 alpha-reductase 2 in human prostate cancer: implications for finasteride therapy of prostate carcinoma. Prostate57, 134–139.PubMedCrossRefGoogle Scholar
  41. Mahoney, E.M. and Harrison, J.H.(1972). Bilateral adrenalectomy for palliative treatment of prostatic cancer. J. Urol.108, 936–938.PubMedGoogle Scholar
  42. Masiello, D., Cheng, S., Bubley, G.J., Lu, M.L., and Balk, S.P.(2002). Bicalutamide functions as an androgen receptor antagonist by assembly of a transcriptionally inactive receptor. J. Biol. Chem.277, 26321–26326.PubMedCrossRefGoogle Scholar
  43. Matsuura, K., Shiraishi, H., Hara, A., Sato, K., Deyashiki, Y., Ninomiya, M., and Sakai, S.(1998). Identification of a principal mRNA species for human 3alpha-hydroxysteroid dehydrogenase isoform (AKR1C3) that exhibits high prostaglandin D2 11-ketoreductase activity. J. Biochem.124, 940–946.PubMedGoogle Scholar
  44. Miyamoto, H., Yeh, S., Lardy, H., Messing, E., and Chang, C.(1998). Delta5-androstenediol is a natural hormone with androgenic activity in human prostate cancer cells. Proc. Natl. Acad. Sci. U. S. A95, 11083–11088.PubMedCrossRefGoogle Scholar
  45. Mizokami, A., Koh, E., Fujita, H., Maeda, Y., Egawa, M., Koshida, K., Honma, S., Keller, E.T., and Namiki, M.(2004). The adrenal androgen androstenediol is present in prostate cancer tissue after androgen deprivation therapy and activates mutated androgen receptor. Cancer Res.64, 765–771.PubMedCrossRefGoogle Scholar
  46. Mohler, J.L., Gregory, C.W., Ford, O.H., III, Kim, D., Weaver, C.M., Petrusz, P., Wilson, E.M., and French, F.S.(2004). The androgen axis in recurrent prostate cancer. Clin. Cancer Res.10, 440–448.PubMedCrossRefGoogle Scholar
  47. Nishiyama, T., Hashimoto, Y., and Takahashi, K.(2004). The influence of androgen deprivation therapy on dihydrotestosterone levels in the prostatic tissue of patients with prostate cancer. Clin. Cancer Res.10, 7121–7126.PubMedCrossRefGoogle Scholar
  48. Page, S.T., Lin, D.W., Mostaghel, E.A., Hess, D.L., True, L.D., Amory, J.K., Nelson, P.S., Matsumoto, A.M., and Bremner, W.J.(2006). Persistent intraprostatic androgen concentrations after medical castration in healthy men. J. Clin. Endocrinol. Metab91, 3850–3856.PubMedCrossRefGoogle Scholar
  49. Pelletier, G., Luu-The, V., Tetu, B., and Labrie, F.(1999). Immunocytochemical localization of type 5 17beta-hydroxysteroid dehydrogenase in human reproductive tissues. J. Histochem. Cytochem.47, 731–738.PubMedCrossRefGoogle Scholar
  50. Penning, T.M., Bauman, D.R., Jin, Y., and Rizner, T.L.(2007). Identification of the molecular switch that regulates access of 5alpha-DHT to the androgen receptor. Mol. Cell Endocrinol. 265–266, 77–82.PubMedCrossRefGoogle Scholar
  51. Penning, T.M., Burczynski, M.E., Jez, J.M., Hung, C.F., Lin, H.K., Ma, H., Moore, M., Palackal, N., and Ratnam, K.(2000). Human 3alpha-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the aldo-keto reductase superfamily: functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones. Biochem. J.351, 67–77.PubMedCrossRefGoogle Scholar
  52. Penning, T.M., Steckelbroeck, S., Bauman, D.R., Miller, M.W., Jin, Y., Peehl, D.M., Fung, K.M., and Lin, H.K.(2006). Aldo-keto reductase (AKR) 1C3: role in prostate disease and the development of specific inhibitors. Mol. Cell Endocrinol.248, 182–191.PubMedCrossRefGoogle Scholar
  53. Ratnam, K., Ma, H., and Penning, T.M.(1999). The arginine 276 anchor for NADP(H) dictates fluorescence kinetic transients in 3 alpha-hydroxysteroid dehydrogenase, a representative aldo-keto reductase. Biochemistry38, 7856–7864.PubMedCrossRefGoogle Scholar
  54. Rizner, T.L., Lin, H.K., Peehl, D.M., Steckelbroeck, S., Bauman, D.R., and Penning, T.M.(2003). Human type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2) and androgen metabolism in prostate cells. Endocrinology144, 2922–2932.PubMedCrossRefGoogle Scholar
  55. Russell, D.W. and Wilson, J.D.(1994). Steroid 5 alpha-reductase: two genes/two enzymes. Annu. Rev. Biochem.63, 25–61.PubMedCrossRefGoogle Scholar
  56. Scher, H.I., Liebertz, C., Kelly, W.K., Mazumdar, M., Brett, C., Schwartz, L., Kolvenbag, G., Shapiro, L., and Schwartz, M.(1997). Bicalutamide for advanced prostate cancer: the natural versus treated history of disease. J. Clin. Oncol.15, 2928–2938.PubMedGoogle Scholar
  57. Shang, Y., Myers, M., and Brown, M.(2002). Formation of the androgen receptor transcription complex. Mol. Cell9, 601–610.PubMedCrossRefGoogle Scholar
  58. Simard, J., Ricketts, M.L., Gingras, S., Soucy, P., Feltus, F.A., and Melner, M.H.(2005). Molecular biology of the 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase gene family. Endocr. Rev.26, 525–582.PubMedCrossRefGoogle Scholar
  59. Soderstrom, T.G., Bjelfman, C., Brekkan, E., Ask, B., Egevad, L., Norlen, B.J., and Rane, A.(2001). Messenger ribonucleic acid levels of steroid 5 alpha-reductase 2 in human prostate predict the enzyme activity. J. Clin. Endocrinol. Metab.86, 855–858.PubMedCrossRefGoogle Scholar
  60. Stanbrough, M., Bubley, G.J., Ross, K., Golub, T.R., Rubin, M.A., Penning, T.M., Febbo, P.G., and Balk, S.P.(2006). Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res.66, 2815–2825.PubMedCrossRefGoogle Scholar
  61. Steckelbroeck, S., Jin, Y., Gopishetty, S., Oyesanmi, B., and Penning, T.M.(2004). Human cytosolic 3alpha-hydroxysteroid dehydrogenases of the aldo-keto reductase superfamily display significant 3beta-hydroxysteroid dehydrogenase activity: implications for steroid hormone metabolism and action. J. Biol. Chem.279, 10784–10795.PubMedCrossRefGoogle Scholar
  62. Swinnen, J.V., Ulrix, W., Heyns, W., and Verhoeven, G.(1997). Coordinate regulation of lipogenic gene expression by androgens: evidence for a cascade mechanism involving sterol regulatory element binding proteins. Proc. Natl. Acad. Sci. U. S. A94, 12975–12980.PubMedCrossRefGoogle Scholar
  63. Thomas, L.N., Douglas, R.C., Vessey, J.P., Gupta, R., Fontaine, D., Norman, R.W., Thompson, I.M., Troyer, D.A., Rittmaster, R.S., and Lazier, C.B.(2003). 5alpha-reductase type 1 immunostaining is enhanced in some prostate cancers compared with benign prostatic hyperplasia epithelium. J. Urol.170, 2019–2025.PubMedCrossRefGoogle Scholar
  64. Thomas, L.N., Lazier, C.B., Gupta, R., Norman, R.W., Troyer, D.A., O'Brien, S.P., and Rittmaster, R.S.(2005). Differential alterations in 5alpha-reductase type 1 and type 2 levels during development and progression of prostate cancer. Prostate63, 231–239.PubMedCrossRefGoogle Scholar
  65. Thomas, L.N., Douglas, R.C., Lazier, C.B., Too, C.K., Rittmaster, R.S., and Tindall, D.J.(2007). Type 1 and Type 2 5alpha-reductase expression in the development and progression of prostate cancer. Eur. Urol.53, 244-252.PubMedCrossRefGoogle Scholar
  66. Thompson, I.M., Goodman, P.J., Tangen, C.M., Lucia, M.S., Miller, G.J., Ford, L.G., Lieber, M.M., Cespedes, R.D., Atkins, J.N., Lippman, S.M., Carlin, S.M., Ryan, A., Szczepanek, C.M., Crowley, J.J., and Coltman, C.A., Jr.(2003). The influence of finasteride on the development of prostate cancer. N. Engl. J. Med.349, 215–224.PubMedCrossRefGoogle Scholar
  67. Titus, M.A., Gregory, C.W., Ford, O.H., III, Schell, M.J., Maygarden, S.J., and Mohler, J.L.(2005a). Steroid 5alpha-reductase isozymes I and II in recurrent prostate cancer. Clin. Cancer Res.11, 4365–4371.CrossRefGoogle Scholar
  68. Titus, M.A., Schell, M.J., Lih, F.B., Tomer, K.B., and Mohler, J.L.(2005b). Testosterone and dihydrotestosterone tissue levels in recurrent prostate cancer. Clin. Cancer Res.11, 4653–4657.CrossRefGoogle Scholar
  69. Weihua, Z., Lathe, R., Warner, M., and Gustafsson, J.A.(2002). An endocrine pathway in the prostate, ERbeta, AR, 5alpha-androstane-3beta,17beta-diol, and CYP7B1, regulates prostate growth. Proc. Natl. Acad. Sci. U. S. A99, 13589–13594.PubMedCrossRefGoogle Scholar
  70. Weihua, Z., Makela, S., Andersson, L.C., Salmi, S., Saji, S., Webster, J.I., Jensen, E.V., Nilsson, S., Warner, M., and Gustafsson, J.A.(2001). A role for estrogen receptor beta in the regulation of growth of the ventral prostate. Proc. Natl. Acad. Sci. U. S. A98, 6330–6335.PubMedCrossRefGoogle Scholar
  71. Wilson, J.D., Griffin, J.E., and Russell, D.W.(1993). Steroid 5 alpha-reductase 2 deficiency. Endocr. Rev.14, 577–593.PubMedGoogle Scholar
  72. Zhu, P., Baek, S.H., Bourk, E.M., Ohgi, K.A., Garcia-Bassets, I., Sanjo, H., Akira, S., Kotol, P.F., Glass, C.K., Rosenfeld, M.G., and Rose, D.W.(2006). Macrophage/Cancer cell interactions mediate hormone resistance by a nuclear receptor derepression pathway. Cell124, 615–629.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Cancer Biology ProgramHematology Oncology DivisionBrookline Avenue BostonUSA

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