PHYTOESTROGENS HAVE AGONISTIC AND COMBINATORIAL EFFECTS ON ESTROGEN-RESPONSIVE GENE-EXPRESSION IN MCF-7 HUMAN BREAST-CANCER CELLS

Phytoestrogens can exhibit agonistic actions on estrogen-dependent gen e expression in breast cancer cells. Since several different phytoestr ogens may be found within a single dietary plant source, we sought to investigate whether estrogen-dependent gene expression may be further influenced by the collective treatment of breast cancer cells with mul tiple phytoestrogens. Accordingly, we transfected MCF-7 breast cancer cells with estrogen-responsive reporters followed by treatment with on e of four phytoestrogens (genistein, daidzein, formononetin, and equol ) or a combination of these in the absence of estradiol. Our results d emonstrated clear-cut agonistic effects of phytoestrogens on estrogen- dependent gene expression. Moreover, combinatorial treatment consisten tly stimulated reporter activity above that observed for individual ph ytoestrogens. Inasmuch as the phytoestrogens tested are frequently fou nd together in food sources, these combinatorial responses may more ac curately reflect the consequences of in vivo exposure.