Mechanisms of 17-beta-estradiol regulation of the proto-oncogene Bcl-2 in MCF-7 human breast cancer cells.

Abstract

In the present studies, the mechanisms of estrogen regulation of Bcl-2 were investigated by analyzing the expression of different Bcl-2 promoter-driven constructs stably transfected into MCF-7 cells. An approximately 1.7 kilobase (kb) sequence which directed estrogen-dependent regulation of Bcl-2 expression in these stable MCF-7 clones was identified. Another agent which may play a role in the regulation of Bcl-2 expression is the tumour suppressor gene, p53. We investigated the effects of various mutant p53 proteins and low levels of p53 on Bcl-2 expression in MCF-7 cells. Neither MCF-7/E6 cells expressing virtually undetectable levels of p53 nor MCF-7/173L cells expressing a DNA binding domain mutant p53, showed altered E2-mediated induction of Bcl-2 mRNA or protein levels. However, MCF-7 cells expressing a truncated mutant p53 protein (Delta291) resulted in a dramatic decrease in Bcl-2 protein levels, but not mRNA levels, upon E2 treatment. These results suggest that a p53 protein lacking a carboxy-terminus may cooperate with E2 post-transcriptionally to negatively regulate Bcl-2 levels in MCF-7 human breast cancer cells. (Abstract shortened by UMI.)