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

Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
Breast Cancer Research and Treatment (Impact Factor: 3.94). 05/2009; 120(2):357-67. DOI: 10.1007/s10549-009-0393-2
Source: PubMed


To investigate a presumed crosstalk between estrogen receptor alpha (ERalpha) and the TGF-beta signaling pathway in breast cancer, we analyzed the TGF-beta-induced expression of the plasminogen activator inhibitor 1 (PAI-1) gene in ER-positive MCF-7 cells. After siRNA-mediated knock-down of endogenous ERalpha, the transcription level of PAI-1 was upregulated, pointing to an attenuation of TGF-beta signaling by the presence of ERalpha. We verified these findings by a vice versa approach using a primary ER-negative cell model transiently overexpressing either ERalpha or ERbeta. We found that ERalpha, but not ERbeta, led to a strong inhibition of the TGF-beta1 signal, monitored by TGF-beta reporter assays. This attenuation was completely independent of receptor stimulation by beta-estradiol (E2) or inhibition by the pure antagonist ICI 182.780 (ICI). Our results indicate a permanent repression of PAI-1 by ERalpha and suggest a ligand-independent crosstalk between ERalpha and TGF-beta signaling in breast cancer cells.

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    • "Eigengene of tricluster 48 is significantly expressed between 0 and 12 hours, 3 and 12 hours. The KEGG pathway term TGF-beta signaling pathway is meliorated in this tricluster and the crosstalk between TGF-beta signaling pathway and ER α has been reported in a previous study [18]. Genes SKP1, BMPR2 are found to play a role in the enriched pathway. "
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