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• W2115028037 abstract "Estrogen drives both transcriptional activation and proteolysis of estrogen receptor alpha (ER alpha; encoded by ESR1). Here we observed variable and overlapping ESR1 mRNA levels in 200 ER alpha-negative and 50 ER alpha-positive primary breast cancers examined, which suggests important posttranscriptional ER alpha regulation. Our results indicate that Src cooperates with estrogen to activate ER alpha proteolysis. Inducible Src stimulated ligand-activated ER alpha transcriptional activity and reduced ER alpha t(1/2). Src and ER alpha levels were inversely correlated in primary breast cancers. ER alpha-negative primary breast cancers and cell lines showed increased Src levels and/or activity compared with ER alpha-positive cancers and cells. ER alpha t(1/2) was reduced in ER alpha-negative cell lines. In both ER alpha-positive and -negative cell lines, both proteasome and Src inhibitors increased ER alpha levels. Src inhibition impaired ligand-activated ER alpha ubiquitylation and increased ER alpha levels. Src siRNA impaired ligand-activated ER alpha loss in BT-20 cells. Pretreatment with Src increased ER alpha ubiquitylation and degradation in vitro. These findings provide what we believe to be a novel link between Src activation and ER alpha proteolysis and support a model whereby crosstalk between liganded ER alpha and Src drives ER alpha transcriptional activity and targets ER alpha for ubiquitin-dependent proteolysis. Oncogenic Src activation may promote not only proliferation, but also estrogen-activated ER alpha loss in a subset of ER alpha-negative breast cancers, altering prognosis and response to therapy." @default.
• W2115028037 created "2016-06-24" @default.
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• W2115028037 date "2007-08-01" @default.
• W2115028037 modified "2023-10-14" @default.
• W2115028037 title "Src promotes estrogen-dependent estrogen receptor α proteolysis in human breast cancer" @default.
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• W2115028037 doi "https://doi.org/10.1172/jci21739" @default.
• W2115028037 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1906730" @default.
• W2115028037 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17627304" @default.
• W2115028037 hasPublicationYear "2007" @default.
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