Abstract
Resistance to anti-estrogen therapy is a major clinical concern in treatment of breast cancer. Estrogen-independent phosphorylation of estrogen receptor alpha, specifically on Ser167, is one of the contributing causes to development of resistance, and a prognostic marker for the disease. Here, we dissect the signaling pathways responsible for Ser167 phosphorylation. We report that the mTOR/S6K1 and MAPK/RSK contribute non-overlapping inputs into ERalpha activation via Ser167 phosphorylation. This cooperation may be targeted in breast cancer treatment by a combination of mTOR and MAPK inhibitors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Breast Neoplasms / drug therapy
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Breast Neoplasms / metabolism
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Cell Line, Tumor
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Estrogen Receptor alpha / metabolism*
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Female
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Humans
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Mitogen-Activated Protein Kinase Kinases / metabolism*
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Phosphorylation
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Protein Kinases / metabolism*
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Ribosomal Protein S6 Kinases, 90-kDa / metabolism*
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Serine / metabolism
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Signal Transduction
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TOR Serine-Threonine Kinases
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Transcription, Genetic
Substances
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ESR1 protein, human
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Estrogen Receptor alpha
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Serine
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Protein Kinases
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MTOR protein, human
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RPS6KA1 protein, human
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Ribosomal Protein S6 Kinases, 90-kDa
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TOR Serine-Threonine Kinases
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Mitogen-Activated Protein Kinase Kinases