Ontology type: schema:ScholarlyArticle Open Access: True
2013-12
AUTHORSWeiyi Toy, Yang Shen, Helen Won, Bradley Green, Rita A Sakr, Marie Will, Zhiqiang Li, Kinisha Gala, Sean Fanning, Tari A King, Clifford Hudis, David Chen, Tetiana Taran, Gabriel Hortobagyi, Geoffrey Greene, Michael Berger, José Baselga, Sarat Chandarlapaty
ABSTRACTSeventy percent of breast cancers express estrogen receptor (ER), and most of these are sensitive to ER inhibition. However, many such tumors for unknown reasons become refractory to inhibition of estrogen action in the metastatic setting. We conducted a comprehensive genetic analysis of two independent cohorts of metastatic ER-positive breast tumors and identified mutations in ESR1 affecting the ligand-binding domain (LBD) in 14 of 80 cases. These included highly recurrent mutations encoding p.Tyr537Ser, p.Tyr537Asn and p.Asp538Gly alterations. Molecular dynamics simulations suggest that the structures of the Tyr537Ser and Asp538Gly mutants involve hydrogen bonding of the mutant amino acids with Asp351, thus favoring the agonist conformation of the receptor. Consistent with this model, mutant receptors drive ER-dependent transcription and proliferation in the absence of hormone and reduce the efficacy of ER antagonists. These data implicate LBD-mutant forms of ER in mediating clinical resistance to hormonal therapy and suggest that more potent ER antagonists may be of substantial therapeutic benefit. More... »
PAGES1439-1445
http://scigraph.springernature.com/pub.10.1038/ng.2822
DOIhttp://dx.doi.org/10.1038/ng.2822
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PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/24185512
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]Download the RDF metadata as: json-ld nt turtle xml License info
JSON-LD is a popular format for linked data which is fully compatible with JSON.
curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/ng.2822'
N-Triples is a line-based linked data format ideal for batch operations.
curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/ng.2822'
Turtle is a human-readable linked data format.
curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/ng.2822'
RDF/XML is a standard XML format for linked data.
curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/ng.2822'
This table displays all metadata directly associated to this object as RDF triples.
408 TRIPLES
21 PREDICATES
84 URIs
39 LITERALS
27 BLANK NODES