Urology
Volume 57, Issue 4, Supplement 1 , Pages 68-72 , April 2001

Selective estrogen receptor modulators for the chemoprevention of prostate cancer

  • Mitchell S Steiner

      Affiliations

    • Department of Urology, University of Tennessee, Memphis, Tennessee, USA (MSS, SR)
    • GTx, Inc., Memphis, Tennessee, USA (MSS)
    • Corresponding Author InformationReprint requests: Mitchell S. Steiner, MD, Department of Urology, University of Tennessee, Memphis, 1211 Union Avenue, Suite 340, Memphis, TN 38104
    • ,
  • Sharan Raghow

      Affiliations

    • Department of Urology, University of Tennessee, Memphis, Tennessee, USA (MSS, SR)
    • ,
  • Blake L Neubauer

      Affiliations

    • Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA (BLN)

References 

  1. Landis SH, Murray T, Bolden S, et al.  Cancer statistics, 1999. CA Cancer J Clin. 1999;49:8–31
  2. Badalament RA, Bahn DK, Lee F. Is radical prostatectomy primarily a surgical debulking procedure?. Urol Oncol. 1996;2:88–91
  3. Kelloff GJ, Lieberman R, Steele VE, et al.  Chemoprevention of prostatic cancer (concepts and strategies). Eur Urol. 1999;35:342–350
  4. Kelloff GJ, Boone CW, Malone WF, et al.  Introductory remarks (development of chemopreventive agents for prostatic cancer). J Cell Biochem Supplement. 1992;16H:1–8
  5. Watanabe T, Inoue S, Ogawa S, et al.  Agonistic effect of tamoxifen is dependent on cell type, ERE-promoter context, and estrogen receptor subtype (functional difference between estrogen receptors alpha and beta). Biochem Biophys Res Commun. 1997;236:140–145
  6. Kuiper GG, Carlsson B, Grandien K, et al.  Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology. 1997;138:863–870
  7. Kuiper GG, Enmark E, Pelto-Huikko M, et al.  Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA. 1996;93:5925–5930
  8. Shughrue PJ, Lane MV, Scrimo PJ, et al.  Comparative distribution of estrogen receptor-alpha (ER-alpha) and beta (ER-beta) mRNA in the rat pituitary, gonad, and reproductive tract. Steroids. 1998;63:498–504
  9. Couse JF, Lindzey J, Grandien K, et al.  Tissue distribution and quantitative analysis of estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta) messenger ribonucleic acid in the wild-type and ERalpha-knockout mouse. Endocrinology. 1997;138:4613–4621
  10. Paech K, Webb P, Kuiper GG, et al.  Differential ligand activation of estrogen receptors ERalpha and ERbeta at AP1 sites. Science. 1997;277:1508–1510[see comments]
  11. Chang WY, Prins GS. Estrogen receptor-beta (implications for the prostate gland). Prostate. 1999;40:115–124
  12. Montano MM, Jaiswal AK, Katzenellenbogen BS. Transcriptional regulation of the human quinone reductase gene by antiestrogen-liganded estrogen receptor-alpha and estrogen receptor-beta. J Biol Chem. 1998;273:25443–25449
  13. Hanstein B, Liu H, Yancisin MC, et al.  Functional analysis of a novel estrogen receptor-beta isoform. Mol Endocrinol. 1999;13:129–137
  14. Petersen DN, Tkalcevic GT, Koza-Taylor PH, et al.  Identification of estrogen receptor beta2, a functional variant of estrogen receptor beta expressed in normal rat tissues. Endocrinology. 1998;139:1082–1092
  15. Ogawa S, Inoue S, Watanabe T, et al.  Molecular cloning and characterization of human estrogen receptor betacx (a potential inhibitor of estrogen action in human). Nucleic Acids Res. 1998;26:3505–3512
  16. Horwitz KB, Jackson TA, Bain DL, et al.  Nuclear receptor coactivators and corepressors. Mol Endocrinol. 1996;10:1167–1177
  17. Griffiths K, Cockett A, Coffey D, et al: Regulation of prostate growth, in Denis L, Griffiths K, Khoury S, Cockett ATK, McConnell J, Chatelain C, Murphy G, Yoshida O, (eds): The 4th International Consultation on Benign Prostatic Hyperplasia. S.C.I., Paris, 1998, pp 83–128.
  18. Prins G. Developmental estrogenization of the prostate gland. In:  Naz R editors. Prostate (Basic and Clinical Aspects). New York: CRC Press; 1997;p. 247–265
  19. Lau KM, Leav I, Ho SM. Rat estrogen receptor-alpha and -beta, and progesterone receptor mRNA expression in various prostatic lobes and microdissected normal and dysplastic epithelial tissues of the Noble rats. Endocrinology. 1998;139:424–427
  20. Krege JH, Hodgin JB, Couse JF, et al.  Generation and reproductive phenotypes of mice lacking estrogen receptor beta. Proc Natl Acad Sci USA. 1998;95:15677–15682
  21. Mosselman S, Polman J, Dijkema R. ER beta (identification and characterization of a novel human estrogen receptor). FEBS Lett. 1996;392:49–53
  22. Ehara H, Koji T, Deguchi T, et al.  Expression of estrogen receptor in diseased human prostate assessed by non-radioactive in situ hybridization and immunohistochemistry. Prostate. 1995;27:304–313
  23. Enmark E, Pelto-Huikko M, Grandien K, et al.  Human estrogen receptor beta-gene structure, chromosomal localization, and expression pattern. J Clin Endocrinol Metab. 1997;82:4258–4265
  24. Brolin J, Skoog L, Ekman P. Immunohistochemistry and biochemistry in detection of androgen, progesterone, and estrogen receptors in benign and malignant human prostatic tissue. Prostate. 1992;20:281–295
  25. Veldscholte J, Ris-Stalpers C, Kuiper GG, et al.  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. 1990;173:534–540
  26. Castagnetta LA, Miceli MD, Sorci CM, et al.  Growth of LNCaP human prostatic cancer cells is stimulated by estradiol via its own receptor. Endocrinology. 1995;136:2309–2319
  27. Carruba G, Pfeffer U, Fecarotta E, et al.  Estradiol inhibits growth of hormone-nonresponsive PC3 human prostatic cancer cells. Cancer Res. 1994;54:1190–1193
  28. Aronica SM, Katzenellenbogen BS. Stimulation of estrogen receptor-mediated transcription and alteration in the phosphorylation state of the rat uterine estrogen receptor by estrogen, cyclic adenosine monophosphate, and insulin-like growth factor-I. Mol Endocrinol. 1993;7:743–752
  29. Bonkhoff H, Fixemer T, Hunsicker I, et al.  Estrogen receptor expression in prostatic cancer and premalignant prostatic lesions. Am J Pathol. 1999;155:641–647
  30. Bodker A, Bruun J, Balslev E, et al.  Estrogen receptors in the human male prostatic urethra and prostate in prostatic cancer and benign prostatic hyperplasia. Scand J Urol Nephrol. 1999;33:237–242
  31. Moore RJ, Gazak JM, Wilson JD. Regulation of cytoplasmic dihydrotestosterone binding in dog prostate by 17b-estradiol. J Clin Invest. 1979;63:351–357
  32. Ho S-M, Lee K-F, Lane K. Neoplastic transformation of the prostate. In:  Naz R editors. Prostate (Basic and Clinical Aspects). New York: CRC Press; 1997;p. 74–114
  33. Blanchere M, Berthaut I, Portois MC, et al.  Hormonal regulation of the androgen receptor expression in human prostatic cells in culture. J Steroid Biochem Mol Biol. 1998;66:319–326
  34. Mobbs BG, Johnson IE, Connolly JG, et al.  Concentration and cellular distribution of androgen receptor in human prostatic neoplasia (can estrogen treatment increase androgen receptor content?). J Steroid Biochem. 1983;19:1279–1290
  35. Cheng E, Lee C, Grayhack J. Endocrinology of the prostate. In:  Lepor H,  Lawson R editor. Prostate Diseases. Philadelphia: WB Saunders; 1993;p. 57–71
  36. Walsh PC, Wilson JD. The induction of prostatic hypertrophy in the dog with androstanediol. J Clin Invest. 1976;57:1093–1097
  37. Prins GS, Marmer M, Woodham C, et al.  Estrogen receptor-beta messenger ribonucleic acid ontogeny in the prostate of normal and neonatally estrogenized rats. Endocrinology. 1998;139:874–883
  38. Arai Y, Mori T, Suzuki Y, Bern HA: Long-term effects of perinatal exposure to sex steroids and diethylstilbestrol on the reproductive system of male mammals, in Bourne JF (ed): International Review of Cytology. New York, Academic Press, 1983 vol 84:235–268.
  39. Pylkkanen L, Makela S, Valve E, et al.  Prostatic dysplasia associated with increased expression of c-myc in neonatally estrogenized mice. J Urol. 1993;149:1593–1601
  40. Shibata Y, Ito K, Suzuki K, et al.  Changes in the endocrine environment of the human prostate transition zone with aging (simultaneous quantitative analysis of prostatic sex steroids and comparison with human prostatic histological composition). Prostate. 2000;42:45–55
  41. Ross R, Bernstein L, Judd H, et al.  Serum testosterone levels in healthy young black and white men. J Natl Cancer Inst. 1986;76:45–48
  42. Leav I, Ho S-M, Ofner P, et al.  Biochemical alterations in sex hormone-induced hyperplasia and dysplasia of the dorsolateral prostates of Noble rats. J Natl Cancer Inst. 1988;80:1045–1053
  43. Leav I, Merk FB, Kwan PW, et al.  Androgen-supported estrogen-enhanced epithelial proliferation in the prostates of intact Noble rats. Prostate. 1989;15:23–40
  44. Ofner P, Bosland MC, Vena RL. Differential effects of diethylstilbestrol and estradiol-17 beta in combination with testosterone on rat prostate lobes. Toxicol Appl Pharmacol. 1992;112:300–309
  45. Mobbs BG, Johnson IE, Liu Y. Quantitation of cytosolic and nuclear estrogen and progesterone receptor in benign, untreated, and treated malignant human prostatic tissue by radioligand binding and enzyme-immunoassays. Prostate. 1990;16:235–244
  46. Habenicht UF, el Etreby MF. The periurethral zone of the prostate of the cynomolgus monkey is the most sensitive prostate part for an estrogenic stimulus. Prostate. 1988;13:305–316
  47. Denis L, Morton MS, Griffiths K. Diet and its preventive role in prostatic disease. Eur Urol. 1999;35:377–387
  48. Price KR, Fenwick GR. Naturally occurring oestrogens in foods (a review). Food Addit Contam. 1985;2:73–106
  49. Levenson AS, Jordan VC. Selective estrogen receptor modulation (molecular pharmacology for the millennium). Eur J Cancer. 1999;35:1974–1985
  50. Lucia MS, Anzano MA, Slatyer MV, et al.  Chemopreventive activity of tamoxifen, N-(4-hydroxyphenyl) retinamide, and the vitamin D analogue Ro24–5531 for androgen-promoted carcinomas of the rat seminal vesicle and prostate. Cancer Res. 1995;55:5621–5627
  51. Pollard M. Prevention of prostate-related cancers in Lobund-Wistar rats. Prostate. 1999;39:305–309
  52. Greenberg NM, DeMayo F, Finegold MJ, et al.  Prostatic cancer in a transgenic mouse. Proc Natl Acad Sci USA. 1995;92:3439–3443
  53. Gingrich JR, Barrios RJ, Morton RA, et al.  Metastatic prostatic cancer in a transgenic mouse. Cancer Res. 1996;56:4096–4102
  54. Gingrich JR, Barrios RJ, Kattan MJ, et al.  Androgen independent prostatic cancer progression in the TRAMP model. Cancer Res. 1997;57:4687–4691
  55. Sato M, Zeng GQ, Rowley E, et al.  LY353381·HCL (an improved benzothiophene analog with bone efficacy complementary to PTH (1-34)). Endocrinology. 1998;139:4642–4651
  56. Ma L, Palkowitz A, Bryant HU, et al. Long term dosing of LY353381. HCL preserves bone quality, reduces turnover and lowers cholesterol levels in ovariectomized rats (abstract). Bone 23 (suppl 5):S609, 1998.
  57. Steiner MS. The role of peptide growth factors in the prostate (a review). Urology. 1993;42:99–110
  58. Steiner MS. Review of peptide growth factors in benign prostatic hyperplasia and urologic malignancy. J Urol. 1995;153:1085–1096
  59. Lam HY. Tamoxifen is a calmodulin antagonist in the activation of cAMP phosphodiestrase. Biochem Biophys Res Commun. 1984;118:27–32
  60. O’Brien CA, Liskamp RM, Solomon DH. Inhibition of protein kinase C by tamoxifen. Cancer Res. 1985;45:2462–2465
  61. Rohlff C, Blagosklonny MV, Kyle E, et al.  Prostatic cancer cell growth inhibition by tamoxifen is associated with inhibition of protein kinase C and induction of p21(waf1/cip1). Prostate. 1998;37:51–59
  62. Tremblay GB, Tremblay A, Copeland NG, et al.  Cloning, chromosomal localization, and functional analysis of the murine estrogen receptor beta. Mol Endocrinol. 1997;11:353–365
  63. Labrie F, Labrie C, Belanger A, et al.  EM-652 (SCH 57068), a third generation SERM acting as pure antiestrogen in the mammary gland and endometrium. J Steroid Biochem Mol Biol. 1999;69:51–84
  64. Black LJ, Goode RL. Uterine bioassay of tamoxifen, trioxifene and a new estrogen antagonist (LY117018) in rats and mice. Life Sci. 1980;26:1453–1458
  65. Simard J, Labrie F. Keoxifene shows pure antiestrogenic activity in pituitary gonadotrophs. Mol Cell Endocrinol. 1985;39:141–144
  66. Buelke-Sam J, Bryant HU, Francis PC. The selective estrogen receptor modulator, raloxifene (an overview of nonclinical pharmacology and reproductive and developmental testing). Reprod Toxicol. 1998;12:217–221
  67. Treinen KA, Rehm S, Wier PJ. An evaluation of the novel selective estrogen receptor modulator, idoxifene, for effects on reproduction in rats and rabbits. Toxicol Sci. 1998;41:199–207
  68. Van Leeuwen FE, Benraadt J, Coebergh JWW. Risk of endometrial cancer after tamoxifen treatment of breast cancer. Lancet. 1994;343:448–452
  69. Rutquist LE, Johansson H. Adjuvant tamoxifen therapy for early stage breast cancer and second primary malignancies. J Nat Cancer Inst. 1995;87:645–651
  70. Hard GC, Iatropoulous MJ, Jordan K. Major difference in the hepatocarcinogenicity and DNA adduct forming ability between toremifene and tamoxifen in female Crl:CD(BR) rats. Cancer Res. 1993;53:4534–4541
  71. Montandon F, Williams GM. Comparison of DNA reactivity of poly-phenylethylene hormonal agents diethylstilbestrol, tamoxifen and toremifene in rat and hamster liver. Arch Toxicol. 1994;68:272–275
  72. White IN, De Matteis F, Davies A. Genotoxic potential of tamoxifen and analogous in female Fischer F334/n rats, DBA/2 and C57BL/6 mice and in human MCL-5 cells. Carcinogenesis. 1992;13:2197–2203
  73. Bruning P, Bonfrer J, Hart A. Tamoxifen, serum lipoproteins and cardiovascular risk. Br J Cancer. 1988;58:497–499
  74. Love RR, Mazees RB, Barden HS. Effect of tamoxifen on bone mineral density in post menopausal women with breast cancer. N Engl J Med. 1992;326:852–856
  75. McDonald CC, Alexander FE, Whyte BW. Cardiac and vascular morbidity in women receiving adjuvant tamoxifen for breast cancer in a randomized trial. BMJ. 1995;311:977–980

PII: S0090-4295(00)00944-4

Urology
Volume 57, Issue 4, Supplement 1 , Pages 68-72 , April 2001

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