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The convergence of hormone regulation and cell cycle in prostate physiology and prostate tumorigenesis

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Abstract

Despite the intense research focused on prostate cancer, it remains the most frequently diagnosed malignancy in men over 40-yr-of-age, and the second most frequent cause of cancer-related deaths in men in the United States (1). In 1990, the National Cancer Institute convened 50 experts and leaders from various disciplines in the prostate cancer field to discuss research directions that would help elucidate the molecular basis of this disease and reduce the incidence and mortality of prostate cancer (2). Critical issues identified at this meeting included the role of androgens and the regulation of cell cycle in prostate tumorigenesis and its progression to androgen-independence. Hormones and cell cycle clearly play important roles in normal and cancerous prostate physiology; however, little information has emerged that clearly delineates their function in the etiology of prostate cancer. Some of the mutational events that occur during prostate tumorigenesis and its progression to androgen-independence involve alterations to normal growth, developmental and apoptotic programs regulated by androgen, and the cell cycle. As such, the delineation of events by which prostate cancer cells circumvent these regulatory mechanisms will be central to our understanding of prostate tumorigenesis and to the development of new modalities to treat this disease. This article is then intended to summarize the functional convergence of androgen regulation and cell cycle in normal prostate physiology and prostate tumorigenesis.

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References

  1. Greenlee, R. T., Hill-Harmon, M. B., Murray, T., and Thun, M. (2001) Cancer statistics. Cancer J. Clin. 51, 15–36.

    Article  CAS  Google Scholar 

  2. Chiarodo, A. (1991) National Cancer Institute roundtable on prostate cancer: future research directions. Cancer Res. 51, 2498–2505.

    PubMed  CAS  Google Scholar 

  3. Sensibar, J. A. (1995) Analysis of cell death and cell proliferation in embryonic stages, normal adult, and aging prostates in human and animals. Micro. Res. Tech. 30, 342–350.

    Article  CAS  Google Scholar 

  4. Veldscholte, J., Berrevoets, C. A., Brinkmann, A. O., Grootegoed, J. A., and Mulder, E. (1992) Anti-androgens and the mutated androgen receptor of LNCaP cells: differential effects on binding affinity, heatshock protein interaction, and transcription activation. Biochemistry 31, 2393–2399.

    Article  PubMed  CAS  Google Scholar 

  5. Ikonen, T., Palvimo, J. J., Kallio, P. J., Reinikainen, P., and Janne, O. A. (1994) Stimulation of androgen-regulated transactivation by modulators of protein phosphorylation. Endocrinology 135, 1359–1366.

    Article  PubMed  CAS  Google Scholar 

  6. 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.

    Article  PubMed  CAS  Google Scholar 

  7. Heinlein, C. A., Ting, H. J., Yeh, S., and Chang, C. (1999) Identification of ARA70 as a ligand-enhanced coactivator for the peroxisome proliferator-activated receptor gamma. J. Biol. Chem. 274, 16147–16152.

    Article  PubMed  CAS  Google Scholar 

  8. Miyamoto, H., Yeh, S., Wilding, G., and Chang, C. (1998) Promotion of agonist activity of antiandrogens by the androgen receptor coactivator, ARA70, in human prostate cancer DU145 cells. Proc. Natl. Acad. Sci. USA 95, 7379–7384.

    Article  PubMed  CAS  Google Scholar 

  9. Gittes, R. F. (1991) Carcinoma of the prostate. N. Engl. J. Med. 324, 236–245.

    Article  PubMed  CAS  Google Scholar 

  10. Palmberg, C., Koivisto, P., Visakorpi, T., and Tammela, T. L. (1999) PSA decline is an independent prognostic marker in hormonally treated prostate cancer. Eur. Urol. 36, 191–196.

    Article  PubMed  CAS  Google Scholar 

  11. Huggins, C. (1965) Two principles in endocrine therapy of cancers: hormone deprival and hormone interference. Cancer Res. 25, 1163–1167.

    PubMed  CAS  Google Scholar 

  12. Mirosevich, J., Bentel, J. M., Zeps, N., Redmond, S. L., D’Antuono, M. F., and Dawkins, H. J. (1999) Androgen receptor expression of proliferating basal and luminal cells in adult murine ventral prostate. J. Endocrinol. 162, 341–350.

    Article  PubMed  CAS  Google Scholar 

  13. Kurita, T., Wang, Y. Z., Donjacour, A. A., Zhao, C., Lydon, J. P., O’Malley, B. W., Isaacs, J. T., Dahiya, R., and Cunha, G. R. (2001) Paracrine regulation of apoptosis by steroid hormones in the male and female reproductive system. Cell Death Differ. 8, 192–200.

    Article  PubMed  CAS  Google Scholar 

  14. Gao, J., Arnold, J. T., and Isaacs, J. T. (2001) Conversion from a paracrine to an autocrine mechanism of androgen-stimulated growth during malignant transformation of prostatic epithelial cells. Cancer Res. 61, 5038–5044.

    PubMed  CAS  Google Scholar 

  15. Noble, R. L. (1982) Prostate carcinoma of the Nb rat in relation to hormones. Int. Rev. Exp. Pathol. 23, 113–159.

    PubMed  CAS  Google Scholar 

  16. Kuiper, G. G., Enmark, E., Pelto-Huikko, M., Nilsson, S., and Gustafsson, J. A. (1996) Cloning of a novel receptor expressed in rat prostate and ovary. Proc. Natl. Acad. Sci. USA 93, 5925–5930.

    Article  PubMed  CAS  Google Scholar 

  17. Leav, I., Lau, K. M., Adams, J. Y., McNeal, J. E., Taplin, M. E., Wang, J., Singh, H., and Ho, S. M. (2001) Comparative studies of the estrogen receptors beta and alpha and the androgen receptor in normal human prostate glands, dysplasia, and in primary and metastatic carcinoma. Am. J. Pathol. 159, 79–92.

    PubMed  CAS  Google Scholar 

  18. Lau, K. M., LaSpina, M., Long, J., and Ho, S. M. (2000) Expression of estrogen receptor (ER)-alpha and ER-beta in normal and malignant prostatic epithelial cells: regulation by methylation and involvement in growth regulation. Cancer Res. 60, 3175–3182.

    PubMed  CAS  Google Scholar 

  19. Pasquali, D., Rossi, V., Esposito, D., Abbondanza, C., Puca, G. A., Bellastella, A., and Sinisi, A. A. (2001) Loss of estrogen receptor beta expression in malignant human prostate cells in primary cultures and in prostate cancer tissues. J. Clin. Endocrinol. Metab. 86, 2051–2055.

    Article  PubMed  CAS  Google Scholar 

  20. 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. USA 98, 6330–6335.

    Article  PubMed  CAS  Google Scholar 

  21. Xie, W., Wong, Y. C., and Tsao, S. W. (2000) Correlation of increased apoptosis and proliferation with development of prostatic intraepithelial neoplasia (PIN) in ventral prostate of the Noble rat. Prostate 44, 31–39.

    Article  PubMed  CAS  Google Scholar 

  22. Wang, Y., Hayward, S. W., Donjacour, A. A., Young, P., Jacks, T., Sage, J., Dahiya, R., Cardiff, R. D., Day, M. L., and Cunha, G. R. (2000) Sex hormone-induced carcinogenesis in Rb-deficient prostate tissue. Cancer Res. 60, 6008–6017.

    PubMed  CAS  Google Scholar 

  23. Ouyang, X. S., Wang, X., Lee, D. T., Tsao, S. W., and Wong, Y. C. (2001) Up-regulation of TRPM-2, MMP-7 and ID-1 during sex hormone-induced prostate carcinogenesis in the Noble rat. Carcinogenesis 22, 965–973.

    Article  PubMed  CAS  Google Scholar 

  24. Asamoto, M., Hokaiwado, N., Cho, Y. M., Takahashi, S., Ikeda, Y., Imaida, K., and Shirai, T. (2001) Prostate carcinomas developing in transgenic rats with SV40 T antigen expression under probasin promoter control are strictly androgen dependent. Cancer Res. 61, 4693–4700.

    PubMed  CAS  Google Scholar 

  25. Visakorpi, T., Hyytinen, E., Koivisto, P., Tanner, M., Keinanen, R., Palmberg, C., Palotie, A., Tammela, T., Isola, J., and Kallioniemi, O. P. (1995) In vivo amplification of the androgen receptor gene and progression of human prostate cancer. Nat. Genet. 9, 401–406.

    Article  PubMed  CAS  Google Scholar 

  26. Taplin, M. E., Bubley, G. J., Shuster, T. D., Frantz, M. E., Spooner, A. E., Ogata, G. K., Keer, H. N., and Balk, S. P. (1995) Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer. N. Engl. J. Med. 332, 1393–1398.

    Article  PubMed  CAS  Google Scholar 

  27. Veldscholte, J., Ris-Stalpers, C., Kuiper, G. G., Jenster, G., Berrevoets, C., Claassen, E., van Rooij, H. C., Trapman, J., Brinkmann, A. O., and Mulder, E. (1990) A mutation in the ligand binding domain of the androgen receptor of human LNCaP cells affects steroid binding characteristics and response to anti-androgens. Biochem. Biophys. Res. Commun. 173, 534–540.

    Article  PubMed  CAS  Google Scholar 

  28. Suzuki, H., Akakura, K., Komiya, A., Aida, S., Akimoto, S., and Shimazaki, J. (1996) Codon 877 mutation in the androgen receptor gene in advanced prostate cancer: relation to antiandrogen withdrawal syndrome. Prostate 29, 153–158.

    Article  PubMed  CAS  Google Scholar 

  29. Tan, J., Sharief, Y., Hamil, K. G., Gregory, C. W., Zang, D. Y., Sar, M., Gumerlock, P. H., deVere White, R. W., Pretlow, T. G., Harris, S. E., Wilson, E. M., Mohler, J. L., and French, F. S. (1997) Dehydroepiandrosterone activates mutant androgen receptors expressed in the androgen-dependent human prostate cancer xenograft CWR22 and LNCaP cells. Mol. Endocrinol. 11, 450–459.

    Article  PubMed  CAS  Google Scholar 

  30. Taplin, M. E., Bubley, G. J., Ko, Y. J., Small, E. J., Upton, M., Rajeshkumar, B., and Balk, S. P. (1999) Selection for androgen receptor mutations in prostate cancers treated with androgen antagonist. Cancer Res. 59, 2511–2515.

    PubMed  CAS  Google Scholar 

  31. Wang, C., Young, W. J., and Chang, C. (2000) Isolation and characterization of the androgen receptor mutants with divergent transcriptional activity in response to hydroxyflutamide. Endocrine 12, 69–76.

    Article  PubMed  CAS  Google Scholar 

  32. Koivisto, P., Kononen, J., Palmberg, C., Tammela, T., Hyytinen, E., Isola, J., Trapman, J., Cleutjens, K., Noordzij, A., Visakorpi, T., and Kallioniemi, O. P. (1997) Androgen receptor gene amplification: a possible molecular mechanism for androgen deprivation therapy failure in prostate cancer. Cancer Res. 57, 314–319.

    PubMed  CAS  Google Scholar 

  33. Miyoshi, Y., Uemura, H., Fujinami, K., Mikata, K., Harada, M., Kitamura, H., Koizumi, Y., and Kubota, Y. (2000) 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.

    Article  PubMed  CAS  Google Scholar 

  34. Bubendorf, L., Kononen, J., Koivisto, P., Schraml, P., Moch, H., Gasser, T. C., Willi, N., Mihatsch, M. J., Sauter, G., and Kallioniemi, O. P. (1999) Survey of gene amplifications during prostate cancer progression by high-throughout fluorescence in situ hybridization on tissue microarrays. Cancer Res. 59, 803–806.

    PubMed  CAS  Google Scholar 

  35. Culig, Z., Hobisch, A., Cronauer, M. V., Radmayr, C., Trapman, J., Hittmair, A., Bartsch, G., and Klocker, H. (1994) Androgen receptor activation in prostatic tumor cell lines by insulin- like growth factor-I, keratinocyte growth factor, and epidermal growth factor. Cancer Res. 54, 5474–5478.

    PubMed  CAS  Google Scholar 

  36. Fan, N. C., Jeung, E. B., Peng, C., Olofsson, J. I., Krisinger, J., and Leung, P. C. (1994) The human gonadotropin-releasing hormone (GnRH) receptor gene: cloning, genomic organization and chromosomal assignment. Mol. Cell. Endocrinol. 103, R1–6.

    Article  PubMed  CAS  Google Scholar 

  37. Lin, D. L., Whitney, M. C., Yao, Z., and Keller, E. T. (2001) Interleukin-6 induces androgen responsiveness in prostate cancer cells through up-regulation of androgen receptor expression. Clin. Cancer Res. 7, 1773–1781.

    PubMed  CAS  Google Scholar 

  38. Sadar, M. D. (1999) Androgen-independent induction of prostate-specific antigen gene expression via cross-talk between the androgen receptor and protein kinase A signal transduction pathways. J. Biol. Chem. 274, 7777–7783.

    Article  PubMed  CAS  Google Scholar 

  39. Craft, N., Shostak, Y., Carey, M., and Sawyers, C. L. (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.

    Article  PubMed  CAS  Google Scholar 

  40. 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.

    Article  PubMed  CAS  Google Scholar 

  41. Abreu-Martin, M. T., Chari, A., Palladino, A. A., Craft, N. A., and Sawyers, C. L. (1999) Mitogen-activated protein kinase kinase kinase 1 activates androgen receptor-dependent transcription and apoptosis in prostate cancer. Mol. Cell. Biol. 19, 5143–5154.

    PubMed  CAS  Google Scholar 

  42. van der Kwast, T. H., Schalken, J., Ruizeveld de Winter, J. A., van Vroonhoven, C. C., Mulder, E., Boersma, W., and Trapman, J. (1991) Androgen receptors in endocrine-therapy-resistant human prostate cancer. Int. J. Cancer 48, 189–193.

    Article  PubMed  Google Scholar 

  43. Wolf, D. A., Herzinger, T., Hermeking, H., Blaschke, D., and Horz, W. (1993) Transcriptional and posttranscriptional regulation of human androgen receptor expression by androgen. Mol. Endocrinol. 7, 924–936.

    Article  PubMed  CAS  Google Scholar 

  44. Quigley, C. A., De Bellis, A., Marschke, K. B., el-Awady, M. K., Wilson, E. M., and French, F. S. (1995) Androgen receptor defects: historical, clinical, and molecular perspectives. Endocr. Rev. 16, 271–321.

    Article  PubMed  CAS  Google Scholar 

  45. Kinoshita, H., Shi, Y., Sandefur, C., Meisner, L. F., Chang, C., Choon, A., Reznikoff, C. R., Bova, G. S., Friedl, A., and Jarrard, D. F. (2000) Methylation of the androgen receptor minimal promoter silences transcription in human prostate cancer. Cancer Res. 60, 3623–3630.

    PubMed  CAS  Google Scholar 

  46. Nakayama, T., Watanabe, M., Suzuki, H., Toyota, M., Sekita, N., Hirokawa, Y., Mizokami, A., Ito, H., Yatani, R., and Shiraishi, T. (2000) Epigenetic regulation of androgen receptor gene expression in human prostate cancers. Lab. Invest. 80, 1789–1796.

    Article  PubMed  CAS  Google Scholar 

  47. Fribourg, A. F., Knudsen, K. E., Strobeck, M. W., Lindhorst, C. M., and Knudsen, E. S. (2000) Differential requirements for ras and the retinoblastoma tumor suppressor protein in the androgen dependence of prostatic adenocarcinoma cells. Cell. Growth. Differ. 11, 361–372.

    PubMed  CAS  Google Scholar 

  48. Lu, S., Tsai, S. Y., and Tsai, M. J. (1997) Regulation of androgen-dependent prostatic cancer cell growth: androgen regulation of CDK2, CDK4, and CKI p16 genes. Cancer Res. 57, 4511–4516.

    PubMed  CAS  Google Scholar 

  49. Lu, S., Liu, M., Epner, D. E., Tsai, S. Y., and Tsai, M. J. (1999) Androgen regulation of the cyclin-dependent kinase inhibitor p21 gene through an androgen response element in the proximal promoter. Mol. Endocrinol. 13, 376–384.

    Article  PubMed  CAS  Google Scholar 

  50. Lu, S., Jenster, G., and Epner, D. E. (2000) Androgen induction of cyclin-dependent kinase inhibitor p21 gene: role of androgen receptor and transcription factor Sp1 complex. Mol. Endocrinol. 14, 753–760.

    Article  PubMed  CAS  Google Scholar 

  51. Aaltomaa, S., Lipponen, P., Eskelinen, M., Ala-Opas, M., and Kosma, V. M. (1999) Prognostic value and expression of p21 (waf1/cip1) protein in prostate cancer. Prostate 39, 8–15.

    Article  PubMed  CAS  Google Scholar 

  52. Chen, Y., Robles, A. I., Martinez, L. A., Liu, F., Gimenez-Conti, I. B., and Conti, C. J. (1996) Expression of G1 cyclins, cyclin-dependent kinases, and cyclin-dependent kinase inhibitors in androgen-induced prostate proliferation in castrated rats. Cell Growth Differ. 7, 1571–1578.

    PubMed  CAS  Google Scholar 

  53. Knudsen, K. E., Arden, K. C., and Cavenee, W. K. (1998) Multiple G1 regulatory elements control the androgen-dependent proliferation of prostatic carcinoma cells. J. Biol. Chem. 273, 20213–20222.

    Article  PubMed  CAS  Google Scholar 

  54. Weinberg, R. A. (1995) The retinoblastoma protein and cell cycle control. Cell 81, 323–330.

    Article  PubMed  CAS  Google Scholar 

  55. Dyson, N. (1998) The regulation of E2F by pRB-family proteins. Genes. Dev. 12, 2245–2262.

    PubMed  CAS  Google Scholar 

  56. Cooney, K. A., Wetzel, J. C., Merajver, S. D., Macoska, J. A., Singleton, T. P., and Wojno, K. J. (1996) Distinct regions of allelic loss on 13q in prostate cancer. Cancer Res. 56, 1142–1145.

    PubMed  CAS  Google Scholar 

  57. Brooks, J. D., Bova, G. S., and Isaacs, W. B. (1995) Allelic loss of the retinoblastoma gene in primary human prostatic adenocarcinomas. Prostate 26, 35–39

    Article  PubMed  CAS  Google Scholar 

  58. Fiedler, U., Ehlers, W., Meye, A., Fussel, S., Faller, G., Schmidt, U., and Wirth, M. P. (2001) LOH analyses in the region of the putative tumour suppressor gene C13 on chromosome 13q13. Anticancer Res. 21, 2341–2350.

    PubMed  CAS  Google Scholar 

  59. Kubota, Y., Fujinami, K., Uemura, H., Dobashi, Y., Miyamoto, H., Iwasaki, Y., Kitamura, H., and Shuin, T. (1995) Retinoblastoma gene mutations in primary human prostate cancer. Prostate 27, 314–230.

    Article  PubMed  CAS  Google Scholar 

  60. Day, M. L., Foster, R. G., Day, K. C., Zhao, X., Humphrey, P., Swanson, P., Postigo, A. A., Zhang, S. H., and Dean, D. C. (1997) Cell anchorage regulates apoptosis through the retinoblastoma tumor suppressor/E2F pathway. J. Biol. Chem. 272, 8125–8128.

    Article  PubMed  CAS  Google Scholar 

  61. French, L. E., Hahne, M., Viard, I., Radlgruber, G., Zanone, R., Becker, K., Muller, C., and Tschopp, J. (1996) Fas and Fas ligand in embryos and adult mice: ligand expression in several immune-privileged tissues and coexpression in adult tissues characterized by apoptotic cell turnover. J. Cell. Biol. 133, 335–343.

    Article  PubMed  CAS  Google Scholar 

  62. English, H. F., Kyprianou, N., and Isaacs, J. T. (1989) Relationship between DNA fragmentation and apoptosis in the programmed cell death in the rat prostate following castration. Prostate 15, 233–250.

    Article  PubMed  CAS  Google Scholar 

  63. Kyprianou, N., and Isaacs, J. T. (1988) Activation of programmed cell death in the rat ventral prostate after castration. Endocrinology 122, 552–562.

    Article  PubMed  CAS  Google Scholar 

  64. Kerr, J. F., Wyllie, A. H., and Currie, A. R. (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer. 26, 239–257.

    PubMed  CAS  Google Scholar 

  65. Wang, H., Grand, R. J., Milner, A. E., Armitage, R. J., Gordon, J., and Gregory, C. D. (1996) Repression of apoptosis in human B-lymphoma cells by CD40-ligand and Bcl-2: relationship to the cell-cycle and role of the retinoblastoma protein. Oncogene 13, 373–379.

    PubMed  CAS  Google Scholar 

  66. Meikrantz, W., and Schlegel, R. (1995) Apoptosis and the cell cycle. J. Cell Bio. 58, 160–174.

    Article  CAS  Google Scholar 

  67. Santana, P., Pena, L. A., Haimovitz-Friedman, A., Martin, S., Green, D., McLoughlin, M., Cordon-Cardo, C., Schuchman, E. H., Fuks, Z., and Kolesnick, R. (1996) Acid sphingomyelinase-deficient human lymphoblasts and mice are defective in radiation-induced apoptosis. Cell 86, 189–199.

    Article  PubMed  CAS  Google Scholar 

  68. Berges, R. R., Furuya, Y., Remington, L., English, H. F., Jacks, T., and Isaacs, J. T. (1993) Cell proliferation, DNA repair, and p53 function are not required for programmed death of prostatic glandular cells induced by androgen ablation. Proc. Natl. Acad. Sci. USA 90, 8910–8914.

    Article  PubMed  CAS  Google Scholar 

  69. Day, M. L., Wu, S., and Basler, J. W. (1993) Prostatic nerve growth factor inducible A gene binds a novel element in the retinoblastoma gene promoter. Cancer Res. 53, 5597–5599.

    PubMed  CAS  Google Scholar 

  70. Talhouk, R. S., Bissell, M. J., and Werb, Z. (1992) Coordinated expression of extracellular matrix-degrading proteinases and their inhibitors regulates mammary epithelial function during involution. J. Cell Biol. 118, 1271–1282.

    Article  PubMed  CAS  Google Scholar 

  71. Tenniswood, M. P., Guenette, R. S., Lakins, J., Mooibroek, M., Wong, P., and Welsh, J. E. (1992) Active cell death in hormone-dependent tissues. Cancer Metastasis Rev. 11, 197–220.

    Article  PubMed  CAS  Google Scholar 

  72. Frisch, S. M., and Screaton, R. A. (2001) Anoikis mechanisms. Curr. Opin. Cell. Biol. 13, 555–562.

    Article  PubMed  CAS  Google Scholar 

  73. Day, M. L., Zhao, X., Vallorosi, C. J., Putzi, M., Powell, C. T., Lin, C., and Day, K. C. (1999) Ecadherin mediates aggregation-dependent survival of prostate and mammary epithelial cells through the retinoblastoma cell cycle control pathway. J. Biol. Chem. 274, 9656–9664.

    Article  PubMed  CAS  Google Scholar 

  74. Ansonoff, M. A., and Etgen, A. M. (1998) Estradiol elevates protein kinase C catalytic activity in the preoptic area of female rats. Endocrinology 139, 3050–3056.

    Article  PubMed  CAS  Google Scholar 

  75. Marino, M., Pallottini, V., and Trentalance, A. (1998) Estrogens cause rapid activation of IP3-PKC-alpha signal transduction pathway in HEPG2 cells. Biochem. Biophys. Res. Comm. 245, 254–258.

    Article  PubMed  CAS  Google Scholar 

  76. Livneh, E., and Fishman, D. D. (1997) Linking protein kinase C to cell-cycle control European. J. Biochem. 248, 1–9.

    CAS  Google Scholar 

  77. Durham, J. P., Butcher, F. R., Teoh, T. S., Miller, R., and Mawhinney, M. G. (1986) Characterization and androgenic regulation of soluble protein kinases and protein phosphorylation in rat ventral prostate gland Arch. Biochem. Biophys. 244, 692–700.

    Article  PubMed  CAS  Google Scholar 

  78. Zhao, X., Gschwend, J. E., Powell, C. T., Foster, R. G., Day, K. C., and Day, M. L. (1997) Retinoblastoma protein-dependent growth signal conflict and caspase activity are required for protein kinase C-signaled apoptosis of prostate epithelial cells. J. Biol. Chem. 272, 22751–22757.

    Article  PubMed  CAS  Google Scholar 

  79. Greenberg, N. M., DeMayo, F., Finegold, M. J., Medina, D., Tilley, W. D., Aspinall, J. O., Cunha, G. R., Donjacour, A. A., Matusik, R. J., and Rosen, J. M. (1995) Prostate cancer in a transgenic mouse. Proc. Natl. Acad. Sci. USA 92, 3439–3443.

    Article  PubMed  CAS  Google Scholar 

  80. Gingrich, J. R., Barrios, R. J., Morton, R. A., Boyce, B. F., DeMayo, F. J., Finegold, M. J., Angelopoulou, R., Rosen, J. M., and Greenberg, N. M. (1996) Metastatic prostate cancer in a transgenic mouse. Cancer Res. 56, 4096–4102.

    PubMed  CAS  Google Scholar 

  81. Eng, M. H., Charles, L. G., Ross, B. D., Chrisp, C. E., Pienta, K. J., Greenberg, N. M., Hsu, C. X., and Sanda, M. G. (1999) Early castration reduces prostatic carcinogenesis in transgenic mice. Urology 54, 1112–1119.

    Article  PubMed  CAS  Google Scholar 

  82. Lu, J., and Danielsen, M. (1998) Differential regulation of androgen and glucocorticoid receptors by retinoblastoma protein. J. Biol. Chem. 273, 31528–31533.

    Article  PubMed  CAS  Google Scholar 

  83. Yeh, S., Miyamoto, H., Nishimura, K., Kang, H., Ludlow, J., Hsiao, P., Wang, C., Su, C., and Chang, C. (1998) Retinoblastoma, a tumor suppressor, is a coactivator for the androgen receptor in human prostate cancer DU145 cells. Biochem. Biophys. Res. Comm. 248, 361–367.

    Article  PubMed  CAS  Google Scholar 

  84. Ling, M. T., Chan, K. W., and Choo, C. K. (2001) Androgen induces differentiation of a human papillomavirus 16 E6/E7 immortalized prostate epithelial cell line. J. Endocrinol. 170, 287–296.

    Article  PubMed  CAS  Google Scholar 

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Davis, J.N., Day, M.L. The convergence of hormone regulation and cell cycle in prostate physiology and prostate tumorigenesis. Mol Biotechnol 22, 129–138 (2002). https://doi.org/10.1385/MB:22:2:129

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