Influence of phytoestrogens on the proliferation and expression of adhesion receptors in human mammary epithelial cells in vitro.

Tumor metastasis is associated with integrin-mediated adhesion and hyaluronan receptor expression. Accumulating evidence suggests that phytoestrogens, which are naturally occurring, plant-derived phytochemicals, could inhibit tumorigenesis during the development of breast cancer. Less is known, however, about the regulation of adhesion receptors by phytoestrogens and, particularly, their potency to influence proliferation of primary human breast cells in comparison with the steroid hormone 17beta-estradiol. Throughout the proliferation experiments, we used primary human mammary epithelial cells from normal tissue that was derived from plastic surgery. For receptor expression (beta1, alpha2, alpha3, CD44), we used the cell line MCF-7. Both investigations were carried out by flow cytometry. The phenotype of primary human mammary epithelial cells was microscopically characterized by analyzing the distribution of ZO-1, cytokeratin and the estrogen receptors alpha and beta. The integrins and the hyaluronan receptor were significantly up-regulated with 17beta-estradiol in human MCF-7 cells. In contrast, genistein and daidzein did not affect the expression at a concentration of 100 micromol/l. In all proliferation experiments with a significant stimulation of the primary human mammary epithelial cell growth due to 17beta-estradiol, in general, genistein and daidzein did not influence S-phase and G2/M-phase cells. Additionally, the stimulative effect of 17beta-estradiol could be inhibited. As the phytoestrogens do not up-regulate adhesion receptors in human breast cells and, regarding proliferation, are able to abolish the stimulatory effect of 17beta-estradiol, we suggest that phytoestrogens could have beneficial effects for the prevention or inhibition of carcinogenesis in hormone-dependent malignancies.