title: mTOR/S6K1 and MAPK/RSK signaling pathways coordinately regulate estrogen receptor alpha serine 167 phosphorylation.
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.
authors.affiliation: Department of Biology, Stern College for Women of Yeshiva University, New York, NY 10016, USA.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Yamnik
authors.forename: Marina K
authors.initials: MK
authors.lastname: Holz
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D014158:Transcription, Genetic
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D012694:Serine; D011494:Protein Kinases; C546842:MTOR protein, human; C069329:RPS6KA1 protein, human; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D058570:TOR Serine-Threonine Kinases; D020929:Mitogen-Activated Protein Kinase Kinases