INDUCTION OF THE DEATH-PROMOTING GENE BAX-ALPHA SENSITIZES CULTURED BREAST-CANCER CELLS TO DRUG-INDUCED APOPTOSIS

Resistance to apoptosis plays an important role in malignancies that a re refractory to chemotherapy treatment. Recently we have shown that t he expression of bax-alpha, a death-promoting member of the bcl-2 fami ly, is down-regulated in breast cancer and have provided evidence that low box expression might contribute to the pathogenesis of breast can cer. In this study we were able to demonstrate the role of this gene i n chemotherapy-induced apoptosis. We transfected bax-alpha into the br east-cancer cell lines R30C and MCF-7 under the control of an inducibl e tetracycline-dependent expression system. Induction of bax-alpha exp ression did not affect viability by itself but strongly increased chem osensitivity to epirubicin. We were able to demonstrate that this sens itization is due to apoptosis. These data might explain the recently p ublished observation that reduced expression of box is associated with poor response rates to chemotherapy in breast cancer. (C) 1996 Wiley- Liss, Inc.