gms | German Medical Science

27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

Crosstalk between estrogen receptors and the TGF- b signalling cascade in MCF-7 cell migration

Meeting Abstract

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  • corresponding author presenting/speaker Daniela Malek - Freie Universität, Berlin, Deutschland
  • Kleuser Burkhard - Freie Universität, Berlin
  • Gust Ronald - Freie Universität, Berlin

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO066

The electronic version of this article is the complete one and can be found online at:

Published: March 20, 2006

© 2006 Malek et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



The metastatic spread of cancer cells is based on their potency to induce proliferation, motility and degradation of extracellular matrix proteins. Especially in breast cancer, it is well established that hormones may contribute to tumour progression. We have previously shown that both transforming growth factor b (TGF-b) and estrogens are potent inductors of chemotaxis in MCF-7 breast cancer cells. But most interestingly, preincubation of MCF-7 with 17-b-estradiol (E2) drastically diminished the ability of TGF-b to evoke chemotaxis. This inhibition could be due to an interaction with Smad proteins, intracellular signal molecules of the TGF-b cascade, as Smad2 and 3 reporter gene activation and Smad2 and 3 phosphorylation were diminished after sensitisation by E2. Here we present that the crosstalk between estrogens and the Smad signalling cascade is mediated by a non-genomic pathway of E2, as an inhibition of TGF-b migration by E2 and, most interestingly, by the pure antiestrogen ICI 182,780 already occurs after 30min of incubation indicating an involvement of non-genomic pathways. In agreement, there is evidence for a function of Gi-protein-coupled receptors as the E2 as well as the ICI 182,780 effect were diminished after preincubation with pertussis toxin. There is increasing evidence that the orphan receptor GPR30 is a possible mediator for membrane estrogen effects. Indeed, TGF-b-induced migration after pre-treatment with E2 could be restored by transfection with GPR30-specific siRNA into MCF-7 cells. Mitogen-activated protein kinase (MAPK) is known to interfere with the Smad signalling cascade and 17-b-estradiol can stimulate MAPK activity in MCF-7 cells. As PD 098,059, an inhibitor of the activation of MAPK kinase (MAPKK), was found to reverse the inhibitory influence of E2 on TGF-b migration, an involvement of the MAPK signalling pathway can be assumed. In conclusion, our results indicate that estrogens can exert their influence on TGF-b-mediated chemotaxis of MCF-7 cells and the TGF-b signal transduction pathway under involvement of membrane associated Gi-Protein-coupled estrogen receptors.