17-Beta-estradiol inhibits transforming-growth-factor-beta-induced MCF-7 cell migration by Smad3-repression.
Motility of malignant cells plays a crucial role for the metastasis of tumours. Both, 17-beta-estradiol and transforming growth factor-beta (TGF-beta), 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-beta-estradiol, the ability of TGF-beta to evoke chemotaxis was drastically diminished. Abrogation of Smad signalling indicated that this pathway is essential for TGF-beta-mediated MCF-7 cell migration. In agreement, pretreatment of MCF-7 cells with 17-beta-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-beta. Thus, these results indicate a controversial role of 17-beta-estradiol on MCF-7 cell migration. 17-Beta-estradiol potently increases the migratory potency of MCF-7 cells, but inhibits TGF-beta-induced migration by an interaction between estrogen receptors and Smad proteins.
Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Str. 2+4, D-14195 Berlin, Germany.
Daniela
D
Malek
Ronald
R
Gust
Burkhard
B
Kleuser
D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004958:Estradiol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D004958:Estradiol