{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hou JY"],"funding":["NCI NIH HHS"],"pagination":["e54103"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3563537"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["8(2)"],"pubmed_abstract":["While the clinical benefit of MEK inhibitor (MEKi)-based therapy is well established in Raf mutant malignancies, its utility as a suppressor of hyperactive MAPK signaling in the absence of mutated Raf or Ras, is an area of ongoing research. MAPK activation is associated with loss of ERα expression and hormonal resistance in numerous malignancies. Herein, we demonstrate that MEKi induces a feedback response that results in ERα overexpression, phosphorylation and transcriptional activation of ER-regulated genes. Mechanistically, MEKi-mediated ERα overexpression is largely independent of erbB2 and AKT feedback activation, but is ERK-dependent. We subsequently exploit this phenomenon therapeutically by combining the ER-antagonist, fulvestrant with MEKi. This results in synergistic suppression "],"journal":["PloS one"],"pubmed_title":["Exploiting MEK inhibitor-mediated activation of ERα for therapeutic intervention in ER-positive ovarian carcinoma."],"pmcid":["PMC3563537"],"funding_grant_id":["CA077263","R01 CA136854","R01 CA077263","K12 CA132783","R01 CA135061","K12CA132783-01A1"],"pubmed_authors":["Rodriguez-Gabin A","Samaweera L","Goldberg GL","Horwitz SB","McDaid HM","Hazan R","Samaraweera L","Hou JY"],"additional_accession":[]},"is_claimable":false,"name":"Exploiting MEK inhibitor-mediated activation of ERα for therapeutic intervention in ER-positive ovarian carcinoma.","description":"While the clinical benefit of MEK inhibitor (MEKi)-based therapy is well established in Raf mutant malignancies, its utility as a suppressor of hyperactive MAPK signaling in the absence of mutated Raf or Ras, is an area of ongoing research. MAPK activation is associated with loss of ERα expression and hormonal resistance in numerous malignancies. Herein, we demonstrate that MEKi induces a feedback response that results in ERα overexpression, phosphorylation and transcriptional activation of ER-regulated genes. Mechanistically, MEKi-mediated ERα overexpression is largely independent of erbB2 and AKT feedback activation, but is ERK-dependent. We subsequently exploit this phenomenon therapeutically by combining the ER-antagonist, fulvestrant with MEKi. This results in synergistic suppression ","dates":{"release":"2013-01-01T00:00:00Z","publication":"2013","modification":"2026-04-07T20:45:35.941Z","creation":"2019-03-26T23:19:39Z"},"accession":"S-EPMC3563537","cross_references":{"pubmed":["23390495"],"doi":["10.1371/journal.pone.0054103"]}}