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dc.contributor.authorBerger, Alice H.en_US
dc.contributor.authorChen, Mingen_US
dc.contributor.authorMorotti, Alessandroen_US
dc.contributor.authorJanas, Justyna A.en_US
dc.contributor.authorNiki, Masaruen_US
dc.contributor.authorBronson, Roderick T.en_US
dc.contributor.authorTaylor, Barry S.en_US
dc.contributor.authorLadanyi, Marcen_US
dc.contributor.authorVan Aelst, Lindaen_US
dc.contributor.authorPoliti, Katerinaen_US
dc.contributor.authorVarmus, Harold E.en_US
dc.contributor.authorPandolfi, Pier Paoloen_US
dc.date.accessioned2014-03-11T02:48:54Z
dc.date.issued2013en_US
dc.identifier.citationBerger, A. H., M. Chen, A. Morotti, J. A. Janas, M. Niki, R. T. Bronson, B. S. Taylor, et al. 2013. “DOK2 Inhibits EGFR-Mutated Lung Adenocarcinoma.” PLoS ONE 8 (11): e79526. doi:10.1371/journal.pone.0079526. http://dx.doi.org/10.1371/journal.pone.0079526.en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11879070
dc.description.abstractSomatic mutations in the EGFR proto-oncogene occur in ~15% of human lung adenocarcinomas and the importance of EGFR mutations for the initiation and maintenance of lung cancer is well established from mouse models and cancer therapy trials in human lung cancer patients. Recently, we identified DOK2 as a lung adenocarcinoma tumor suppressor gene. Here we show that genomic loss of DOK2 is associated with EGFR mutations in human lung adenocarcinoma, and we hypothesized that loss of DOK2 might therefore cooperate with EGFR mutations to promote lung tumorigenesis. We tested this hypothesis using genetically engineered mouse models and find that loss of Dok2 in the mouse accelerates lung tumorigenesis initiated by oncogenic EGFR, but not that initiated by mutated Kras. Moreover, we find that DOK2 participates in a negative feedback loop that opposes mutated EGFR; EGFR mutation leads to recruitment of DOK2 to EGFR and DOK2-mediated inhibition of downstream activation of RAS. These data identify DOK2 as a tumor suppressor in EGFR-mutant lung adenocarcinoma.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0079526en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3821857/pdf/en
dash.licenseLAAen_US
dc.titleDOK2 Inhibits EGFR-Mutated Lung Adenocarcinomaen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dash.depositing.authorChen, Mingen_US
dc.date.available2014-03-11T02:48:54Z
dc.identifier.doi10.1371/journal.pone.0079526*
dash.authorsorderedfalse
dash.contributor.affiliatedChen, Ming
dash.contributor.affiliatedBronson, Roderick


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