BCL-2 EXPRESSION CONFERS ANDROGEN INDEPENDENCE IN ANDROGEN SENSITIVE PROSTATIC-CARCINOMA

Expression of the bcl-2 proto-oncogene is associated with the progress ion of prostate cancer to androgen-independence. Dunning R3327G (DG) c ells were engineered to express high levels of bcl-2 protein. The pare ntal DG (DG-P) cell line and bcl-2 transfectant (DG-B) clones were gro wn as subcutaneous tumor explants in male athymic nude mice. The rate of tumor growth after castration was significantly lower in DG-P tumor s but was unaffected in DG-B tumors. The proliferative indices (PI) in DG-P and DG-B tumors were similar, however, apoptotic indices (ApI) w ere significantly lower in DG-B tumors before castration. Following ca stration the PI and ApI decreased significantly in DG-P but not DG-B t umors. Bar upregulation was not observed in the DG-P or DG-B tumors, b ut did occur in the ventral prostate, after castration. These findings support a role for bcl-2 expression in conferring androgen-independen t growth during prostate cancer progression.