bcl-2 Suppresses Expression of p21 WAF1/CIPJ in Breast Epithelial Cells'

The tumor suppressor gene p53 regulates G1 checkpoint prior to the initiation of DNA synthesis, which can either induce G1 arrest or signal apoptosis. The involvement ofp53 in apoptosis may also be related to its ability to down-regulate transcription of the bcl-2 gene. The bcl-2 gene product prevents most types of apoptotic cell death, suggesting that bcl-2 interferes with an essential signaling molecule involved in the apoptotic cell death pathway. Although the bcl-2 protein is shown to be overex pressed in many types of human tumor including breast cancer, its biochemical or pathological consequences are poorly understood. To de termine the effects of bcl-2 overexpression on apoptosis and transforma lion of breast epithelial cells and to investigate whether bcl-2 interferes with the p53 pathway, we introduced the bcl-2 expression vector into MCF1OA cells, which were derived from diploid human breast epithelial cells containing the wild-typeps3 gene. Overexpression ofbcl-2 prevented free radical-induced apoptosis and induced a partially transformed phe notype in MCF1OA cells. Although overexpression of bcl-2 did not affect the expression of the p53 gene, p53-dependent gene transcription such as @2jWA@G@'1 was suppressed. These results suggest that bcl-2 may inhibit p53 functional activity and is involved in the regulation of an early commitment step either to proliferate or suicide.