17-β-estradiol inhibits transforming-growth-factor-β-induced MCF-7 cell migration by Smad3-repression

Motility of malignant cells plays a crucial role for the metastasis of tumours. Both, 17-β-estradiol and transforming growth factor-β (TGF-β), induce migration of MCF-7 breast cancer cells and simultaneous treatment resulted in an additive effect of the migratory response. But most interestingly, when cells were preincubated with 17-β-estradiol, the ability of TGF-β to evoke chemotaxis was drastically diminished. Abrogation of Smad signalling indicated that this pathway is essential for TGF-β-mediated MCF-7 cell migration. In agreement, pretreatment of MCF-7 cells with 17-β-estradiol resulted in a reduced phosphorylation of Smad2 and Smad3 as well as a diminished Smad2 and Smad3 gene reporter activity in response to TGF-β. Thus, these results indicate a controversial role of 17-β-estradiol on MCF-7 cell migration. 17-β-estradiol potently increases the migratory potency of MCF-7 cells, but inhibits TGF-β-induced migration by an interaction between estrogen receptors and Smad proteins.