Estrogen and antiestrogen actions on transforming growth factorbeta (TGFbeta) in normal human breast epithelial (HBE) cells.

We have previously shown that estradiol (E2) increases the growth of normal human breast epithelial (HBE) cells and the antiestrogen 4-hydroxytamoxifen (4-OHT) inhibits estrogen-induced proliferation. These effects of estrogens and antiestrogens on proliferation have also been well documented in breast cancer cells. One mechanism for the antiproliferative effects of antiestrogens is the stimulation of TGFbeta in hormone-dependent MCF-7 and T47D cells. The role of this inhibitory growth factor in normal human breast cells has not been well studied. Accordingly, we measured the amounts of total and active TGFbeta1 and TGFbeta2 by specific E(max) immunoassay (EIA) in culture medium from normal breast cells (epithelial and fibroblasts) and from various ER- and ER+ breast cancer cell lines. We established that HBE cells are sensitive to the antiproliferative effect of TGFbetas, and studied the effect of E2 and 4-OHT, alone or in combination, on the secretion and activation of TGFbetas by HBE cells. HBE cells secrete TGFbeta1 and even more TGFbeta2, and are sensitive to these factors. However, in contrast to MCF-7 cells, TGFbeta secretion in normal breast cells is not regulated by E2 and 4-OHT.