EXPRESSION OF THE BCL-2 GENE FAMILY IN NORMAL AND MALIGNANT BREAST-TISSUE - LOW BAX-ALPHA EXPRESSION IN TUMOR-CELLS CORRELATES WITH RESISTANCE TOWARDS APOPTOSIS

We have studied the expression of the apoptosis-regulating genes bcl-2, bcl-x, box and APO-1/fas (CD95) in human breast cancer. The expression pattern of these genes in human breast-cancer tissues and breast-cancer-derived cell lines was compared to that seen in normal breast epithelium and breast epithelial cell lines. No difference with regard to bcl-2 and bcl-x(L) expression was observed between normal breast epithelium and tumor tissue or breast cancer and non-malignant epithelial cell lines. In contrast, bax-alpha, a splice variant of box, which promotes apoptosis, is expressed in high amounts in normal cell lines and breast tissue, whereas only weak or no expression could be detected in cancer-cell lines and malignant tissue. In contrast to malignant cell lines, which express low levels of bax-alpha, non-malignant epithelial cell lines displaying high amounts of box-alpha were highly sensitive to induction of programmed cell death by both serum starvation and APO-1/fas (CD95) triggering. We therefore propose that dysregulation of apoptosis contributes to the pathogenesis of breast cancer, at least in part, due to an imbalance between anti-apoptosis genes (such as bcl-2/bcl-x) and apoptosis-promoting genes (box). (C) 1995 Wiley-Liss, Inc.