DIETARY ESTROGENS ACT THROUGH ESTROGEN RECEPTOR-MEDIATED PROCESSES AND SHOW NO ANTIESTROGENICITY IN CULTURED BREAST-CANCER CELLS

Dietary estrogens are believed to exert their estrogenic or antiestrog enic (chemopreventive) action in estrogen responsive cells by interact ing with the estrogen receptor (ER). The present study was undertaken to evaluate a direct role of ER in estrogenic or antiestrogenic activi ties of three dietary estrogens (coumestrol, genistein and zearalenone ). HeLa cells were transiently co-transfected with an expression vecto r for ER and an estrogen-responsive reporter gene construct. Coumestro l, genistein, and zearalenone all increased the activity of the report er gene, only in the presence of the ER, and the activation was blocke d with the ER antagonist ICI 164,384, demonstrating an ER-specific, ag onist response. In addition, in MCF-7 cells, coumestrol and zearalenon e increased the expression of the estrogen-responsive pS2 gene. Coumes trol and genistein inhibited the purified estrogen-specific 17 beta-hy droxysteroid oxidoreductase enzyme and the conversion of estrone to 17 beta-estradiol in T-47D cells, which contain this enzyme. However, th ey did not inhibit the estrone-induced proliferation of T-47D cells. I n conclusion, coumestrol, genistein, and zearalenone are all potent es trogens in vitro, and they act through ER mediated mechanism. Our find ings give no evidence to support the idea that these compounds act as antiestrogens through competition for the binding sites of ER or by in hibition of the conversion of estrone to 17 beta-estradiol in breast c ancer cells, since this effect was nullified by their agonist action o n cell proliferation. Therefore, their suggested chemopreventive actio n in estrogen-related cancers must be mediated through other mechanism s.