Tamoxifen-induced apoptosis in breast cancer cells relates to down-regulation of bcl-2, but not bax and bcl-X-L, without alteration of p53 protein levels

Tamoxifen (TAM) has been shown to induce apoptosis in breast cancer cells. bcl-2 family genes, which can interact with each other, have been shown to interfere with apoptosis after various stimuli. In this study, we investiga ted the effects of TAM on bcl-2 family gene products bcl-2, bar, and bcl-X- L and on p53 levels in estrogen receptor-positive MCF-7 breast cancer cells . We found that TAM induced time- and concentration-dependent down-regulati on of bcl-2 at both the mRNA and protein level, Down-regulation of bcl-2 co rrelated with TAM-induced apoptosis, In addition, estradiol treatment signi ficantly increased bcl-2 protein expression and blocked the reduction of bc l-2 by TAM, TAM did not, however, affect bar, bcl-X-L, or p53 expression at the mRNA or protein level. Our results demonstrate that TAM can induce apo ptosis in a time- and dose-dependent manner by modulating bcl-2 levels in b reast cancer cells, and downregulation of bcl-2 induced by TAM was not acco mpanied by alterations in p53 levels.