Abstract
Many studies have reported proliferative, differentiating or protective effects of estradiol, notably through estrogen receptor alpha (ERα). On the contrary, the ligand-independent action of ERα is currently poorly documented notably in cell protection. The stable transfection of wild type, substituted or truncated form of ERα in PC12 cells (ERα negative cell line) lead the specific study of its ligand-independent action. Hence, we demonstrate here that, in the absence of E2, the expression of ERα prevents cells from apoptosis induced by serum deprivation. This protection is not due to an ERE-mediated transcription and does not require either AF-1 or AF-2 transactivation functions. It is afforded to the Y537 residue of ERα and activation of c-Src/Stat3 signaling pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis
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Cell Survival
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Estrogen Receptor alpha / chemistry
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Estrogen Receptor alpha / metabolism*
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Humans
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Ligands
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MCF-7 Cells
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PC12 Cells
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Proto-Oncogene Proteins pp60(c-src) / metabolism
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Rats
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STAT3 Transcription Factor / metabolism
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Serum / metabolism*
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Signal Transduction
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Tyrosine / metabolism
Substances
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Estrogen Receptor alpha
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Ligands
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STAT3 Transcription Factor
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Tyrosine
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Proto-Oncogene Proteins pp60(c-src)
Grants and funding
This work was supported by grants from Agence National de la Recherche (http://www.agence-nationale-recherche.fr/; project NEED: CES 2008-011), CRITT-Santé Bretagne (http://www.critt-sante.fr/; contract: 08007968) and INERIS (http://www.ineris.fr/; project NEMO: 189). The authors also thank the CNRS and the University of Rennes I to support their work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.