Estrogen and antiestrogen actions on transforming growth factor beta (Tgf beta) 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-hydroxytamoxife n (4-OHT) inhibits estrogen-induced proliferation. These effects of estroge ns and antiestrogens on proliferation have also been well documented in bre ast cancer cells. One mechanism for the antiproliferative effects of anties trogens is the stimulation of TFG beta in hormone-dependent MCF-7 and T47D cells. The role of this inhibitory growth factor in normal human breast cel ls has not been well studied. Accordingly, we measured the amounts of total and active TGF beta1 and TGF beta2 by specific E-max immunoassay (EIA) in culture medium from normal breast cells (epithelial and fibroblasts) and fr om various ER - and ER + breast cancer cell lines. We established that HBE cells are sensitive to the antiproliferative effect of TCF betas, and studi ed the effect of E2 and 4-OHT, alone or in combination, on the secretion an d activation of TGF betas by HBE cells HBE cells secrete TGF beta1 and even more TGF beta2, and are sensitive to these factors. However. in contrast t o MCF-7 cells, TGF beta secretion in normal breast cells is not regulated b y E2 and 4-OHT. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.