Apoptosis in Relation to Androgen Independence in Experimental and Clinical Prostate Cancer
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).
KeywordsCyproterone Acetate LHRH Agonist Androgen Suppression Androgen Withdrawal Flare Reaction
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