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rdf:type |
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lifeskim:mentions |
umls-concept:C0026882,
umls-concept:C0031715,
umls-concept:C0031727,
umls-concept:C0069515,
umls-concept:C0242957,
umls-concept:C0683598,
umls-concept:C1274040,
umls-concept:C1414313,
umls-concept:C1443775,
umls-concept:C1514562,
umls-concept:C1879547,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221
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pubmed:issue |
1
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pubmed:dateCreated |
2006-7-17
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pubmed:abstractText |
HER2/Neu gene mutations have been identified in lung cancer. Expression of a HER2 mutant containing a G776(YVMA) insertion in exon 20 was more potent than wild-type HER2 in associating with and activating signal transducers, phosphorylating EGFR, and inducing survival, invasiveness, and tumorigenicity. HER2(YVMA) transphosphorylated kinase-dead EGFR(K721R) and EGFR(WT) in the presence of EGFR tyrosine kinase inhibitors (TKIs). Knockdown of mutant HER2 in H1781 lung cancer cells increased apoptosis and restored sensitivity to EGFR TKIs. The HER2 inhibitors lapatinib, trastuzumab, and CI-1033 inhibited growth of H1781 cells and cells expressing exogenous HER2(YVMA). These data suggest that (1) HER2(YVMA) activates cellular substrates more potently than HER2(WT); and (2) cancer cells expressing this mutation remain sensitive to HER2-targeted therapies but insensitive to EGFR TKIs.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal, Humanized,
http://linkedlifedata.com/resource/pubmed/chemical/CI1033,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Morpholines,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Quinazolines,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, erbB-2,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/erlotinib,
http://linkedlifedata.com/resource/pubmed/chemical/gefitinib,
http://linkedlifedata.com/resource/pubmed/chemical/trastuzumab
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1535-6108
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
25-38
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:16843263-Animals,
pubmed-meshheading:16843263-Antibodies, Monoclonal,
pubmed-meshheading:16843263-Antibodies, Monoclonal, Humanized,
pubmed-meshheading:16843263-Apoptosis,
pubmed-meshheading:16843263-Cell Line, Tumor,
pubmed-meshheading:16843263-Cell Movement,
pubmed-meshheading:16843263-Cell Proliferation,
pubmed-meshheading:16843263-Drug Resistance, Neoplasm,
pubmed-meshheading:16843263-Epidermal Growth Factor,
pubmed-meshheading:16843263-Female,
pubmed-meshheading:16843263-Humans,
pubmed-meshheading:16843263-Mice,
pubmed-meshheading:16843263-Mice, Nude,
pubmed-meshheading:16843263-Models, Biological,
pubmed-meshheading:16843263-Morpholines,
pubmed-meshheading:16843263-Mutation,
pubmed-meshheading:16843263-Phosphorylation,
pubmed-meshheading:16843263-Protein Kinase Inhibitors,
pubmed-meshheading:16843263-Quinazolines,
pubmed-meshheading:16843263-RNA, Small Interfering,
pubmed-meshheading:16843263-Receptor, Epidermal Growth Factor,
pubmed-meshheading:16843263-Receptor, erbB-2,
pubmed-meshheading:16843263-Transforming Growth Factor alpha,
pubmed-meshheading:16843263-Xenograft Model Antitumor Assays
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pubmed:year |
2006
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pubmed:articleTitle |
HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors.
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pubmed:affiliation |
Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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