Background: The significance of apoptosis with regard to the development and progression of androgen-dependent cells has not been clearly understood. In the present study we investigated the expression of the bcl-2 proto-oncogene 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 line cloned from Shionogi carcinoma 115 (SC115). The expression of bcl-2 mRNA and protein in SC2G cells was measured by reverse transcription-polymerase chain reaction and western blotting, respectively. We also investigated the effects of antisense oligodeoxynucleotides (ODN) complementary to strategic 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 those without testosterone after 3 days. Apoptosis was demonstrated in approximately 30% of positive-staining nuclei in SC2G cells cultured in testosterone-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 self-programmed apoptosis of androgen-dependent cells, suggesting the possibility of an antisense therapy for hormone-refractory prostate cancer, which is reported to express high levels of Bcl-2 protein.