Tyrosine kinase inhibitors reduce bcl-2 expression and induce apoptosis inandrogen-dependent cells

The signal transduction pathway showing how androgen withdrawal induces apo ptosis in androgen-dependent cells has not been clearly understood. In thes e studies, we focused on the behavior of tyrosine kinases in androgen-depen dent cells and investigated its correlation with apoptosis and bcl-2 expres sion. We used SC2G, an androgen-dependent mouse mammary carcinoma cell line , which had been cloned from Shionogi Carcinoma 115 (SC115). When SC2G cell s were cultured with herbimycin A (HMA), a potent tyrosine kinase inhibitor , the number of viable cells decreased significantly after 24 h. Terminal d eoxyribonucleotidyltransferase-mediated dUTP-biotin nick end labeling and f low cytometric analysis of annexin V staining showed that HMA induced apopt osis of SC2G cells. The level of bcl-2 mRNA in SC2G cells was suppressed by HMA in a dose-dependent manner on RT-PCR. Preincubation with caspase inhib itors protected HMA-induced apoptosis of SC2G cells. When a human bcl-2 gen e was transfected in SC2G cells and overexpressed, SC2G cells seemed to acq uire tolerance for HMA. These data indicate that HMA-sensitive tyrosine kin ase(s) can regulate apoptosis and inhibit bcl-2 expression in SC2G mouse an drogen-dependent cells. Tyrosine kinase(s) seemed to be a mem ber of signal transduction between androgen receptor activation and bcl-2 expression.