Suppression of default apoptosis in androgen-dependent cells by testosterone-mediated bcl-2 expression

Background: The significance of apoptosis with regard to the development an d progression of androgen-dependent cells has not been clearly understood. In the present study we investigated the expression of the bcl-2 proto-onco gene after androgen deprivation and its role in cell growth in an androgen- dependent cell line. Methods: We used SC2G, an androgen-dependent mouse mammary carcinoma cell l ine cloned from Shionogi carcinoma 115 (SC115). The expression of bcl-2 mRN A and protein in SC2G cells was measured by reverse transcription-polymeras e chain reaction and western blotting, respectively. We also investigated t he effects of antisense oligodeoxynucleotides (ODN) complementary to strate gic sites in the mouse bcl-2 gene in SC2G cells. Results: When SC2G cells were cultured in serum-free medium, the number of viable cells was significantly larger among cells with testosterone than th ose without testosterone after 3 days. Apoptosis was demonstrated in approx imately 30% of positive-staining nuclei in SC2G cells cultured in testoster one-free medium. The levels of bcl-2 mRNA and protein in SC2G cells started to decrease after testosterone withdrawal. The cell density of SC2G cells decreased after 4 days culture with antisense ODN when compared with cells cultured in the presence of sense control. Conclusions: These data indicate that bcl-2 proto-oncogene inhibits the sel f-programmed apoptosis of androgen-dependent cells, suggesting the possibil ity of an antisense therapy for hormone-refractory prostate cancer, which i s reported to express high levels of Bcl-2 protein.