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dc.contributor.authorRajurkar, Mihir
dc.contributor.authorde Jesus-Monge, Wilfredo E.
dc.contributor.authorDriscoll, David R.
dc.contributor.authorAppleman, Victoria A.
dc.contributor.authorHuang, He
dc.contributor.authorCotton, Jennifer
dc.contributor.authorKlimstra, David
dc.contributor.authorZhu, Lihua
dc.contributor.authorSimin, Karl
dc.contributor.authorXu, Lan
dc.contributor.authorMcMahon, Andrew P.
dc.contributor.authorLewis, Brian
dc.contributor.authorMao, Junhao
dc.date.accessioned2012-04-11T13:45:55Z
dc.date.issued2012
dc.identifier.citationRajurkar, Mihir, Wilfredo E. de Jesus-Monge, David R. Driscoll, Victoria A. Appleman, He Huang, Jennifer L. Cotton. Forthcoming. Gli transcriptional activity is essential for Kras-induced pancreatic tumorigenesis and regulates IKBKE/NF-\(\kappa\)B activity in the tumor epithelium. Proceedings of the National Academy of Science.en_US
dc.identifier.issn1091-6490en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:8531456
dc.description.abstractPancreatic ductal adenocarcinoma (PDAC), one of the most aggressive human malignances, is thought to be initiated by KRAS activation. Here we find that transcriptional activation mediated by the Gli family of transcription factors, although dispensable for pancreatic development, is required for Kras-induced proliferation and survival in primary pancreatic epithelial cells in culture, and Kras-driven pancreatic intraepithelial neoplasia and PDAC formation in vivo. Further, ectopic Gli1 activation in the mouse pancreas accelerates Kras-driven tumor formation, underscoring the importance of Gli transcription factors in pancreatic tumorigenesis. Interestingly, we demonstrate Gli-stimulated IKBKE (IKK\(\varepsilon\))/nuclear factor-\(\kappa\)B (NF-\(\kappa\)B) activity in pancreatic cancer cells in culture and in vivo, and show that this activity is a critical downstream mediator for Gli-dependent PDAC cell transformation and survival. Together, these studies demonstrate for the first time the requirement for Gli in Kras- dependent pancreatic epithelial transformation, implicate a novel mechanism of Gli-NF-\(\kappa\)B oncogenic activation, and provide genetic evidence supporting the therapeutic targeting of Gli activity in pancreatic cancer.en_US
dc.description.sponsorshipMolecular and Cellular Biologyen_US
dc.language.isoen_USen_US
dc.publisherNational Academy of Scienceen_US
dash.licenseOAP
dc.titleGli Transcriptional Activity Is Essential for Kras-Induced Pancreatic Tumorigenesis and Regulates IKBKE/NF-\(\kappa\)B Activity in the Tumor Epitheliumen_US
dc.typeJournal Articleen_US
dc.description.versionAccepted Manuscripten_US
dc.relation.journalProceedings of the National Academy of Sciencesen_US
dash.depositing.authorMcMahon, Andrew P.
dc.date.available2012-04-11T13:45:55Z
dash.authorsorderedfalse
dash.contributor.affiliatedMcMahon, Andrew P.


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