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dc.contributor.authorChen, Tzu-Hsiu
dc.contributor.authorFeng, Whei
dc.contributor.authorJänne, Pasi A
dc.contributor.authorAlvarez, James V
dc.contributor.authorZappaterra, Mauro
dc.contributor.authorBulmer, Sara E
dc.contributor.authorSellers, William R
dc.contributor.authorGreulich, Heidi E.
dc.contributor.authorFrank, David Alan
dc.contributor.authorHahn, William C.
dc.contributor.authorMeyerson, Matthew Langer
dc.date.accessioned2011-04-28T07:17:13Z
dc.date.issued2005
dc.identifier.citationGreulich, Heidi, Tzu-Hsiu Chen, Whei Feng, Pasi A. Jänne, James V. Alvarez, Mauro Zappaterra, Sara E. Bulmer, et al. 2005. Oncogenic Transformation by Inhibitor-Sensitive and -Resistant EGFR Mutants. PLoS Medicine 2(11): e313.en_US
dc.identifier.issn1549-1277en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4878949
dc.description.abstractBackground: Somatic mutations in the kinase domain of the epidermal growth factor receptor tyrosine kinase gene EGFR are common in lung adenocarcinoma. The presence of mutations correlates with tumor sensitivity to the EGFR inhibitors erlotinib and gefitinib, but the transforming potential of specific mutations and their relationship to drug sensitivity have not been described. Methods and Findings: Here, we demonstrate that EGFR active site mutants are oncogenic. Mutant EGFR can transform both fibroblasts and lung epithelial cells in the absence of exogenous epidermal growth factor, as evidenced by anchorage-independent growth, focus formation, and tumor formation in immunocompromised mice. Transformation is associated with constitutive autophosphorylation of EGFR, Shc phosphorylation, and STAT pathway activation. Whereas transformation by most EGFR mutants confers on cells sensitivity to erlotinib and gefitinib, transformation by an exon 20 insertion makes cells resistant to these inhibitors but more sensitive to the irreversible inhibitor CL-387,785. Conclusion: Oncogenic transformation of cells by different EGFR mutants causes differential sensitivity to gefitinib and erlotinib. Treatment of lung cancers harboring EGFR exon 20 insertions may therefore require the development of alternative kinase inhibition strategies.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pmed.0020313en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240052/pdf/en_US
dash.licenseLAA
dc.subjectcancer biologyen_US
dc.subjectcell biologyen_US
dc.subjectoncologyen_US
dc.subjectcancer: lungen_US
dc.titleOncogenic Transformation by Inhibitor-Sensitive and -Resistant EGFR Mutantsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Medicineen_US
dash.depositing.authorGreulich, Heidi E.
dc.date.available2011-04-28T07:17:13Z
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dash.affiliation.otherHMS^Pathologyen_US
dc.identifier.doi10.1371/journal.pmed.0020313*
dash.authorsorderedfalse
dash.contributor.affiliatedGreulich, Heidi
dash.contributor.affiliatedMeyerson, Matthew
dash.contributor.affiliatedFrank, David
dash.contributor.affiliatedHahn, William


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