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Estrogen receptor α attenuates transforming growth factor-β signaling in breast cancer cells independent from agonistic and antagonistic ligands

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Abstract

To investigate a presumed crosstalk between estrogen receptor α (ERα) and the TGF-β signaling pathway in breast cancer, we analyzed the TGF-β-induced expression of the plasminogen activator inhibitor 1 (PAI-1) gene in ER-positive MCF-7 cells. After siRNA-mediated knock-down of endogenous ERα, the transcription level of PAI-1 was upregulated, pointing to an attenuation of TGF-β signaling by the presence of ERα. We verified these findings by a vice versa approach using a primary ER-negative cell model transiently overexpressing either ERα or ERβ. We found that ERα, but not ERβ, led to a strong inhibition of the TGF-β1 signal, monitored by TGF-β reporter assays. This attenuation was completely independent of receptor stimulation by β-estradiol (E2) or inhibition by the pure antagonist ICI 182.780 (ICI). Our results indicate a permanent repression of PAI-1 by ERα and suggest a ligand-independent crosstalk between ERα and TGF-β signaling in breast cancer cells.

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Acknowledgments

This work was supported by grants from the Robert Bosch Foundation.

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Authors and Affiliations

  1. Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany

    Matthias B. Stope, Simone L. Popp & Miriam B. Buck

  2. Department of Clinical Chemistry, Robert Bosch Hospital, Auerbachstrasse 110, 70376, Stuttgart, Germany

    Cornelius Knabbe

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  1. Matthias B. Stope
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  2. Simone L. Popp
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  3. Cornelius Knabbe
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  4. Miriam B. Buck
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Correspondence to Cornelius Knabbe.

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Stope, M.B., Popp, S.L., Knabbe, C. et al. Estrogen receptor α attenuates transforming growth factor-β signaling in breast cancer cells independent from agonistic and antagonistic ligands. Breast Cancer Res Treat 120, 357–367 (2010). https://doi.org/10.1007/s10549-009-0393-2

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  • DOI: https://doi.org/10.1007/s10549-009-0393-2

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