Bcl-2 Expression In The Prostate And Its Association With Androgen-Independent Prostate Cancer

Le résumé fourni par la source

Prostate cancer is now the most commonly diagnosed malignancy in American men, surpassing even carcinoma of the lung. Most patients have advanced disease at the time of diagnosis and are, therefore, not considered candidates for potentially curative surgical resection. The most effective frontline therapy for these patients currently is androgen ablation. The initial biologic consequence of this therapy is to induce programmed cell death in the responsive prostatic cancer cells ( Kyprianou et al ., 1990 ). It is unfortunate that virtually all patients will experience rapidly fatal, androgen-independent tumour recurrences for which there remains no effective therapy. Tumor recurrence is thought to represent the clonal selection of pre-existing, androgen-independent cells ( Sinha et al ., 1977 ; Kyprianou et al ., 1990 ; Roehrborn et al ., 1991 ; Van Weerden, 1991 ). Numerous investigators have established experimentally that this hormonal ablation results in the death of over 80% of the prostatic epithelial cells by the derepression of an endogenous programmed cell death cascade ( Isaacs, 1984 ; English et al , 1985 , 1989 ; Kyprianou and Isaacs, 1988 ; Kyprianou et al. , 1990 ). Activation of this cascade has been shown to be associated with the enhanced expression of specific genes. The upregulation of genes, such as TGF-β and TRPM-2, has been shown to immediately precede the onset of programmed cell death in the prostate and has been implicated in the mediation of this process ( Montpetit et al ., 1986 ; Buttyan et al ., 1989 ; Kyprianou and Isaacs, 1989 ; Kyprianou et al ., 1990 ). The molecular basis for the emergence of androgen-independent prostate cancer is, as yet, poorly understood. It is reasonable to assume that understanding the molecular regulation of androgendependent programmed cell death in the prostate will provide insights into the basis for the development of androgen-independent prostate cancer as well as suggest additional approaches for therapeutic intervention.

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