Apoptosis in Relation to Androgen Independence in Experimental and Clinical Prostate Cancer

  • P. S. Rennie
  • N. Bruchovsky
  • K. Akakura
  • S. L. Goldenberg
  • M. Gleave
  • L. Sullivan
Conference paper
Part of the Ernst Schering Research Foundation Workshop book series (SCHERING FOUND, volume 14)

Abstract

In the prostate and other androgen-dependent tissues, androgens govern the expression of three types of regulatory genes during the growth and differentiation of stem cells (Bruchovsky et al. 1975). Initiation of DNA synthesis is an example of one type — positive gene regulation by androgens; whereas inhibition of these processes in the presence of a rising titer of hormone typifies another type — negative gene regulation. The third type is exemplified by induction of autophagic lysis (apoptosis) after withdrawal of androgens and involves the expression of a number of androgen-repressed genes (Montpetit et al. 1986; Rennie et al. 1984, 1988). By definition, the third type accounts for androgen dependence. Usually both positive and androgen-repressed types of gene regulation are manifested in androgen-dependent tumors (Bruchovsky et al. 1987). In an androgen-poor environment, most cells in an androgen-dependent tumor undergo apoptosis. However, surviving tumorigenic stem cells irreversibly progress to an androgen-independent condition and give rise to a recurrent tumor with a greatly increased population of androgen-independent stem cells (Bruchovsky et al. 1990).

Keywords

Toxicity Testosterone Flare Expense Androgen 

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References

  1. Akakura K, Bruchovsky N, Goldenberg SL, Rennie PS, Buckley AR, Sullivan LD (1993) Effects of intermittent androgen suppression on androgen-dependent tumors. Cancer 71: 2782–2790PubMedCrossRefGoogle Scholar
  2. Bettuzzi S, Hiipakka RA, Gilna P, Liao S (1989) Identification of an androgenrepressed mRNA in rat ventral prostate as coding for sulphated glycoprotein 2 by cDNA cloning and sequence analysis. Biochem J 257: 293–296PubMedGoogle Scholar
  3. Bruchovsky N, Lesser B, Van Doom E, Craven S (1975) Hormonal effects on cell proliferation in rat prostate. Vitam Horm 33: 61–102PubMedCrossRefGoogle Scholar
  4. Bruchovsky N, Brown EM, Coppin CM, Goldenberg SL, Le Riche JC, Murray NC, Rennie PS (1987) The endocrinology and treatment of prostate tumor progression. In: Coffey DS, Bruchovsky N, Gardner WA Jr, Resnick MI, Karr JP (eds) Current concepts and approaches to the study of prostate cancer. Liss, New York, pp 347–387Google Scholar
  5. Bruchovsky N, Rennie PS, Coldman AJ, Goldenberg SL, To M, Lawson D (1990) Effects of androgen withdrawal on the stem cell composition of the Shionogi carcinoma. Cancer Res 50: 2275–2282PubMedGoogle Scholar
  6. Bruchovsky N, Goldenberg SL, Akakura K, Rennie PS (1993) LHRH agonists in prostate cancer: elimination of flare reaction by pretreatment with cyproterone acetate and low-dose diethylstilbestrol. Cancer 72: 1685–1691Google Scholar
  7. Buttyan R, Olsson CA, Pintar J, Chang C, Bandyk M, Ng P, Sawczuk IS (1989) Induction of the TRPM-2 gene in cells undergoing programmed death. Mol Cell Biol 9: 3473–3481PubMedGoogle Scholar
  8. Gleave M, Hsieh J-T, Wu HC, von Eschenbach AC, Chung LWK (1992) Serum prostate specific antigen levels in mice bearing human prostate LNCaP tumors are determined by tumor volume and endocrine and growth factors. Cancer Res 52: 1598–1605PubMedGoogle Scholar
  9. Klotz LH, Kerr HW, Morse MJ, Whitmore WF Jr (1986) Intermittent endocrine therapy for advanced prostate cancer. Cancer 58: 2546–2550PubMedCrossRefGoogle Scholar
  10. Montpetit ML, Lawless KR, Tenniswood M (1986) Androgen-repressed messages in the rat ventral prostate. Prostate 8: 25–36PubMedCrossRefGoogle Scholar
  11. Rennie PS, Bouffard R, Bruchovsky N, Cheng H (1984) Increased activity of plasminogen activators during involution of the rat ventral prostate. Biochem J 221: 171–178PubMedGoogle Scholar
  12. Rennie PS, Bruchovsky N, Buttyan R, Benson M, Cheng H (1988) Gene expression during the early phases of regression of the androgen-dependent Shionogi mouse mammary carcinoma. Cancer Res 48: 6309–6312PubMedGoogle Scholar
  13. Tenniswood MP, Guenette RS, Lakins J, Mooibroek M, Wong P, Welsh J-E (1992) Active cell death in hormone-dependent tissues. Cancer Metastasis Rev 11: 197–220PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • P. S. Rennie
  • N. Bruchovsky
  • K. Akakura
  • S. L. Goldenberg
  • M. Gleave
  • L. Sullivan

There are no affiliations available

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