Biochemistry of Prostate Cancer

  • F. K. Habib

Abstract

Research on the prostate and other male accessory sexual organs is producing new insights into the regulatory mechanisms responsible for the normal and abnormal growth of the prostate. This chapter is an attempt to review some of the most recent developments in both fundamental and clinical research on the endocrinology of the human prostate and to highlight the significance of the findings on the long-term management of prostate cancer.

Keywords

Adenocarcinoma Testosterone Polypeptide Androgen Oestradiol 

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References

  1. Andersson S, Russell DW (1990) Structural and biochemical properties of cloned and expressed human ras steroid 5a-reductases Proc Natl Acad Sci USA 87: 3640–3644Google Scholar
  2. Andersson S, Birman DM, Jenkins EP, Russell DW (1991) A deletion of steroid 5a-reductase 2 gene in male pseudohermaphroditism. Nature 354: 159–161PubMedCrossRefGoogle Scholar
  3. Bookstein R, Shew JY, Chen PL et al. (1990) Suppression of tumorigenicity of human prostate carcinoma cells by replacing a mutated RB gene. Science 247: 712–715PubMedCrossRefGoogle Scholar
  4. Brinkmann AO, Trapman J (1992) Androgen receptor mutants that affect normal growth and development. Cancer Surv 14: 95–111PubMedGoogle Scholar
  5. Brinkmann AO, Kuiper GGJM, Ris-Stalpers C et al. (1991) Androgen receptor abnormalities Steroid Biochem Mol Biol 40: 349–352CrossRefGoogle Scholar
  6. British Prostate Group Study (1979) Evaluation of plasma hormone concentrations in relation to clinical staging in patients with prostate cancer. Br J Cancer 51: 382–389Google Scholar
  7. Chackal-Roy M, Niemeyer C, Moore M et al. (1989) Stimulation of human prostatic carcinoma cell growth by factors present in human bone marrow. J Clin Invest 84: 43–50PubMedCrossRefGoogle Scholar
  8. Chang C, Kokontis J, Liao S (1988) Molecular cloning of human and rat complementary DNA encoding androgen receptors. Science 240: 324–326PubMedCrossRefGoogle Scholar
  9. Chaproniere DM, McKeehan WL (1986) Serial culture of single adult prostatic epithelial cells in serum free medium containing low calcium and a new growth factor from bovine brain. Cancer Res 46: 819–824PubMedGoogle Scholar
  10. Chodak GW, Crane DM, Libertad AP et al. (1992) A nuclear localisation of androgen receptor in heterogenous samples of normal, hyperplastic and neoplastic human prostate. J Urol 147: 798–803PubMedGoogle Scholar
  11. Cunha JR, Dontjacour AA, Cooke PS et al. (1987). The endocrinology and developmental biology of the prostate. Endocrinol Rev 8: 338–363CrossRefGoogle Scholar
  12. Dave JR, Witorsch RJ (1985) Prolactin increases lipid fluidity and prolactin binding of rat prostatic membranes. Am J Physiol 248: E687PubMedGoogle Scholar
  13. Farnsworth WE (1990) Prolactin. In: Farnsworth WE, Ablin RG (eds) The prostate as an endocrine gland. CRC Press, Boca Raton, FL, pp 177–185Google Scholar
  14. Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61: 759–767PubMedCrossRefGoogle Scholar
  15. Gelmann EP (1991) Oncogenes and growth factors in prostate cancer. J NIH Res 3: 62–64Google Scholar
  16. George FW, Russell DW, Wolfson JD (1991) Feed–forward control of prostate growth: dihydrotestosterone induces expression of its own biosynthetic enzyme, steriod 5a–reductase. Proc Nat Acad Sci USA 88: 8044–8047PubMedCrossRefGoogle Scholar
  17. Gleave ME, Hsieh JT, Gao C et al. (1991) Acceleration of human prostate cancer growth in vivo by factors produced by prostate and bone fibroblast. Cancer Res 51: 3753–3761PubMedGoogle Scholar
  18. Gregory H, Wilshire IR, Cavanagh JP et al. (1986) Urogastrone - epidermal growth factor concentration prostatic fluid of normal individuals and patients with benign prostatic hypertrophy. Clin Sci 70: 359–363PubMedGoogle Scholar
  19. Griffin JE, Wilson JD (1992) Disorders of the testis and the male reproductive tract. In: Wilson JD, Foster DW (eds) Williams textbook of endocrinology 8th edn, W.B. Saunders, Philadelphia, pp 799–851Google Scholar
  20. Habib FK, (1990) Prostate mechanisms of normal and abnormal metabolism. In: Chisholm GD, Fair WR (eds) Scientific foundations of urology, 3rd edn. Heinemann Medical, London, pp 358–365Google Scholar
  21. Habib FK, Chisholm GD (1991) The role of growth factors in the human prostate. Scand J Nephrol 126: 53–58Google Scholar
  22. Habib FK, Busuttil A, Robinson RA, Chisholm GD (1985) 5a–reductase activity in human prostate cancer is related to the histological differentiation of the tumour. Clin Endocrinol 23: 431–438Google Scholar
  23. Habib FK, Odoma S, Busuttil A, Chisholm GD (1986) Androgen receptors in cancer of the prostate: correlation with the stage and grade of the tumour on receptor content. Cancer 57: 2351–2356PubMedCrossRefGoogle Scholar
  24. Hay ED (1987) Cell matrix interaction in the embryo: cell shape, cell surface and their role in differentiation. In: Trelstad RL (ed) The role of extra cellular matrix in development. Alan R Liss, New York, pp 1–31Google Scholar
  25. Hofer DR, Sherwood ER, Bromberg WD et al. (1991) Autonomous growth of androgen-independent human prostatic carcinoma cells: role of transforming growth factor a. Cancer Res 51: 2780–2785PubMedGoogle Scholar
  26. Huggins C, Hodges CV (1941) Studies on prostate cancer I. Effect of castration, of oestrogen and of androgen injection on serum phosphatase in the metastatic carcinoma of the prostate. Cancer Res 1: 293–297Google Scholar
  27. Isaacs JT, Coffey DS (1981) Adaptation versus selection on the mechanism responsible for the relapse of prostatic cancer to androgen ablation therapy as studied in the R–3327–H adenocarcinoma. Cancer Res 41: 5070–5075PubMedGoogle Scholar
  28. Isaacs WB, Carter BS, Ewing CM (1991) While type p53 suppresses growth of human prostate cancer cells containing mutant p53 alleles. Cancer Res 51: 4716–4720PubMedGoogle Scholar
  29. Jacobi GH, Interhauf K, Kurth KH et al. (1978) Bromocriptine and prostatic carcinoma: the plasmid kinetics, production and tissue uptake of radiolabeled testosterone in vivo. J Urol 119: 240–243PubMedGoogle Scholar
  30. James R, Bradshaw RA (1984) Polypeptide growth factors. Annu Rev Biochem 53: 259–292PubMedCrossRefGoogle Scholar
  31. Jenkins EP, Andersson S, Imperato-McGinley J, Wilson JD, Russell DW (1992) Genetic and pharmacological evidence for more than one human steroid 5a–reductase. J Clin Invest 89: 293–300PubMedCrossRefGoogle Scholar
  32. Kaighn ME, Reddel RR, Lechnar JF et al. (1989) Transformation of human neonatal prostate epithelial cells by strontium phosphate transfection with a plasmid containing SV40 earlier lesion genes. Cancer Res 49: 3050–3057PubMedGoogle Scholar
  33. Koutsilieris M, Robbani SA, Goltzman D (1987) The effects of human prostatic mitogens on rat bone cells and fibroblast. J Endocrinol 115: 447–454PubMedCrossRefGoogle Scholar
  34. Kumar V, Green S, Staub A, Chambon P (1986) Localisation of the oestradiol binding and putative DNA binding domains of the human oestrogen receptor. EMBO J 5: 2231–2236PubMedGoogle Scholar
  35. Kyprianou N, Isaacs JT (1988) Identification of a cellular receptor for transforming growth factor ß in rat ventral prostates and its negative regulation by androgens. Endocrinology 123: 2124–2131PubMedCrossRefGoogle Scholar
  36. Lang SH, Miller WR, Duncan W, Habib FK (1994) The role of granulocyte macrophage-colony stimulating factor and erythropoietin in prostate cancer. Cancer Res (in press)Google Scholar
  37. Leake A, Chisholm GD, Habib FK (1984) Interaction between prolactin and zinc in the human prostate gland. J Endocrinol 102: 73–76PubMedCrossRefGoogle Scholar
  38. Lubahn DB, Joesph DR, Sullivan PM, Willard HF, French FS, Wilson EM (1988) Cloning of human androgen receptor complementary cDNA and localisation on the X chromosome. Science 240: 327–330PubMedCrossRefGoogle Scholar
  39. MacDonald A, Habib FK (1992) Divergent responses to epidermal growth factor in hormone sensitive and insensitive human prostate cancer cell lines. Br J Cancer 65: 177–182PubMedCrossRefGoogle Scholar
  40. MacDonald A, Chisholm GD, Habib FK (1990) Production and response of a human prostatic cancer line to transforming growth factor-like molecules. Br J Cancer 62: 579–584PubMedCrossRefGoogle Scholar
  41. Maddy SQ, Chisholm GD, Hawkins RA, Habib FK (1987) Localization of epidermal growth factor receptors in the human prostate by biochemical and immunocytochemical methods. J Endocrinol 113: 147–153PubMedCrossRefGoogle Scholar
  42. Maddy SO, Chisholm GD, Busuttil A, Habib FK (1989) Epidermal growth factor receptors in human prostate cancer: correlation with histological differentiation of the tumour. Br J Cancer 60: 41–44PubMedCrossRefGoogle Scholar
  43. Mansson PE, Adams P, Kan M et al. (1989) Heparin–binding growth factor gene expression and receptor characteristics in normal rat prostate and two transplantable rat prostate tumours. Cancer Res 49: 2485–2494PubMedGoogle Scholar
  44. Massague J (1990) Transforming growth factor ß family. Annu Rev Cell Biol 6: 597–641PubMedCrossRefGoogle Scholar
  45. Massague J (1992) Receptors for TGFß family. Cell 69: 1067–1070PubMedCrossRefGoogle Scholar
  46. Mee ED, Khan O, Mashiti K (1984) High serum prolactin associated with poor prognosis in carcinoma of the prostate. Br J Urol 56: 698–701PubMedCrossRefGoogle Scholar
  47. Mellon K, Thomson S, Charlton RG et al. (1992) p53, C-erbB-2 and the epidermal growth facor receptor in the benign and malignant prostate. J Urol 147: 496–499PubMedGoogle Scholar
  48. Montgomery BJ, Young CWF, Bilhartz DL et al. (1992) Hormonal regulation of prostate specific antigen (PSA) glycoprotein in the human prostate adenocarcinoma cell line, LNCaP. Prostate 21: 63–73PubMedCrossRefGoogle Scholar
  49. Mori HM, Maki K, Oishi M et al. (1990) Increased expression of genes for basic fibroblast growth factor and transforming growth factor type ß-2 in human benign prostatic hyperplasia. Prostate 16: 71–80PubMedCrossRefGoogle Scholar
  50. Muller WJ, Lee FS, Dickson C, Peters G, Pattingale P, Leder P (1990) The int-2 gene product acts as an epithelial growth factor in transgenic mice. EMBO J 9: 907–913PubMedGoogle Scholar
  51. Mydlo JH, Macchia RJ (1992) Growth factors in urologic tissues: detection, characterization, and clinical applications. Urology 40: 491–498PubMedCrossRefGoogle Scholar
  52. Mydlo JH, Bulbul MA, Richon VM et al. (1988) Heparin binding growth factor isolated from human prostate extracts. Prostate 12: 343–355PubMedCrossRefGoogle Scholar
  53. Odoma S, Chisholm GD, Nicol K, Habib FK (1985) Evidence for the association between blood prolactin and androgen receptors in BPH. J Urol 133: 717–720PubMedGoogle Scholar
  54. Ross RK, Bernstein L, Lobo RA et al. (1992) 5a-reductase activity and risk of prostate cancer among Japanese and US white and black males. Lancet 339: 887–889PubMedCrossRefGoogle Scholar
  55. Sandberg A A (1992) Chromosomal abnormalities and related events in prostate cancer. Hum Pathol 23: 368–380PubMedCrossRefGoogle Scholar
  56. Sandgran EP, Luetteke NC, Palmitar RD et al. (1990) Over expression of TGFa in transgenic mice: induction of epithelial hyperplasia, pancreatic metaplasia and carcinoma of the breast. Cell 61: 1211–1235Google Scholar
  57. Sargent NSE, Habib FK (1991) Partial purification of human prostatic 5a–reductase (3-oxo-5a- steroid: NADP+ 4-ene-oxido-reductase; EC 1.3.1.22) in a stable and active form. J Steroid Biochem Mol Biol 38: 73–77PubMedCrossRefGoogle Scholar
  58. Schuurmans ALG, Bolt J, Mulder E (1988) Androgens in transforming growth factor ß modulate the growth response to epidermal growth factor in human prostate tumour cells ( LNCaP ). Mol Cell Endocrinol 60: 101–104Google Scholar
  59. Sheth NA, Vanaga GR, Hurkadly KS et al. (1987) The prostate — an extra gonadal source of inhibin: demonstration of inhibin in normal, benign, malignant human prostate and rat prostate by bioassay, immunoassay, immunocytochemical localisation and biosynthesis. In: Sheth AR (ed) Inhibins, chemistry, measurement and physiology CRC Press, Boca Raton, FL, pp 109–132Google Scholar
  60. Sibley PEC, Harper ME, Peeling WB et al. (1984) Growth hormone and prostatic tumour localisation using a monoclonal human growth hormone antibody. J Endocrinol 103: 311–315PubMedCrossRefGoogle Scholar
  61. Sporn MB, Roberts AB (1988) Peptide growth factors are multifunctional. Nature 332: 217–219PubMedCrossRefGoogle Scholar
  62. Story MT (1991) Polypeptide modulators of prostatic growth and development. Cancer Surv 11: 123–145PubMedGoogle Scholar
  63. Thigpen AE, Davis DL, Milatovich A et al. (1992) Molecular genetics of steroid 5a-reductase to deficiency. J Clin Invest 90: 799–809PubMedCrossRefGoogle Scholar
  64. Thomson TC (1990) Growth factors and oncogenes in prostate cancer. Cancer Cells 2: 345–354Google Scholar
  65. Tilley WD, Wilson CM, Marcelli M, McPhaul MJ (1990) Androgen receptor gene expression in human prostate carcinoma cell lines. Cancer Res 50: 5382–5386PubMedGoogle Scholar
  66. Traish AM, Wotiz HH (1987) Prostatic epidermal growth factor receptors and irregulation by androgens. Endocrinology 121: 1461–1467PubMedCrossRefGoogle Scholar
  67. Tsai SY, Tsai MY, O’Malley BW (1991) The steroid receptor super family: transactivators of gene expression. In: Parker MG (ed) Nuclear hormone receptors. Academic Press, London, pp 103–124Google Scholar
  68. Veldscholte J, Ris-Stalpars C, Kuiper JG et al. (1990) Invitation to ligand binding domain of the androgen receptor human LNCaP cells affects steroid binding characteristic and responses to anti androgens. Biochem Biophys Res Commun 173: 534–540PubMedCrossRefGoogle Scholar
  69. Visakorpi T, Kallioniemi P, Heikkinen A et al. (1992) Small sub-group of aggressive, highly proliferative prostatic carcinomas defined by p53 accumulation. J Natl Cancer Inst 84: 883–887PubMedCrossRefGoogle Scholar
  70. Weinberg RA (1989) Oncogenes, anti-oncogenes and the molecular basis of multi-step carcinogenesis. Cancer Res 49: 3713–3721PubMedGoogle Scholar
  71. Wilding GE, Valverius E, Knabbe C, Gelmann EP (1989a) The role of transforming growth factor a in human prostate cancer cell growth. Prostate 15: 1–12PubMedCrossRefGoogle Scholar
  72. Wilding G, Zugmeier G, Knabbe C (1989b) Differential effects of transforming growth factor ß on human prostate cancer cells in vitro. Mol Cell Endocrinol 62: 79–87PubMedCrossRefGoogle Scholar
  73. Yong CYF, Qiu SD, Prescott JL, Tindali DJ (1990) Over expression of a partial human androgen receptor in E coli: characterisation of steroid binding, DNA binding and immunological properties. Mol Endocrinol 4: 1841–1849Google Scholar
  74. Yuan S, Trachtenberg J, Mills GB et al. (1993) Androgen induced inhibition of cell proliferation in an androgen-insensitive prostate cancer cell line (PC-3) transfected with a human androgen receptor complementary DNA. Cancer Res 53: 1304–1311PubMedGoogle Scholar

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© Springer-Verlag London Limited 1994

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  • F. K. Habib

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