Hormonal regulation of apoptosis in breast cells and tissues

Few studies have referred to the implication of apoptotic processes followi ng hormonal treatment. No data are available on the effects of progesterone in breast cells. In order to gain insights on the effects of the gonadal s teroids and antiestrogens in breast cells, we have carried out studies on a poptosis in different breast materials. We have developed a model of normal breast cells in cultures that remain hormone-dependent. On these cells and in some hormone-dependent breast cancer cell lines (T-47-D, ZR75-1, MCF-7) we have observed an antiapoptotic effect of estradiol (E-2) and a potent p roapoptotic effect of some antiestrogens. Progestins were also proapoptotic in normal as well as in hormone-dependent breast cancer cells. In order to understand the mechanisms of these hormones on apoptosis, we studied the b cl-2 family proteins, We demonstrated that E-2 increased the antiapoptotic proteins, bcl-2 and bclx(L), whereas, the progestins drastically decreased bcl-2 expression and weakly bclx(L) levels. We investigated the mechanisms by which E-2 increased bcl-2 expression Our results using quantitative RT-P CR showed that E-2 increased bcl-2 mRNA levels at 48 h of treatment via a t ranscriptional mechanism. None of the hormone treatments altered the proapo ptotic protein levels, bax and bak. We also studied the in vivo expression of bcl-2 and other members of its family in biopsies of normal breast tissu es according to the menstrual cycle. Bcl-2 displayed a strong cyclical vari ation and seemed to be the most hormone-dependent member of the family. (C) 2000 Elsevier Science Inc. All rights reserved.