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dc.contributor.authorSnijders, Antoine M.en_US
dc.contributor.authorLiu, Yueyongen_US
dc.contributor.authorSu, Lien_US
dc.contributor.authorHuang, Yurongen_US
dc.contributor.authorMao, Jian-Huaen_US
dc.date.accessioned2016-04-01T15:47:45Z
dc.date.issued2015en_US
dc.identifier.citationSnijders, Antoine M., Yueyong Liu, Li Su, Yurong Huang, and Jian-Hua Mao. 2015. “Expression profiling reveals transcriptional regulation by Fbxw7/mTOR pathway in radiation-induced mouse thymic lymphomas.” Oncotarget 6 (42): 44794-44805.en
dc.identifier.issn1949-2553en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:26318572
dc.description.abstractThe tumor suppressor gene FBXW7 is deleted and mutated in many different types of human cancers. FBXW7 primarily exerts its tumor suppressor activity by ubiquitinating different oncoproteins including mTOR. Here we used gene transcript profiling to gain a deeper understanding of the role of FBXW7 in tumor development and to determine the influence of mTOR inhibition by rapamycin on tumor transcriptome and biological functions. In comparison to tumors from p53 single heterozygous (p53+/−) mice, we find that radiation-induced thymic lymphomas from Fbxw7/p53 double heterozygous (Fbxw7+/−p53+/−) mice show significant deregulation of cholesterol metabolic processes independent of rapamycin treatment, while cell cycle related genes were upregulated in tumors from placebo treated Fbxw7+/−p53+/− mice, but not in tumors from rapamycin treated Fbxw7+/−p53+/− mice. On the other hand, tumors from rapamycin treated Fbxw7+/−p53+/− mice were enriched for genes involved in the integrated stress response, an adaptive mechanism to survive in stressful environments. Finally, we demonstrated that the Fbxw7 gene signatures identified in mouse tumors significantly overlap with FBXW7 co-expressed genes in human cancers. Importantly these common FBXW7 gene signatures between mouse and human are predictive for disease-free survival in human colon, breast and lung adenocarcinoma cancer patients. These results provide novel insights into the role of FBXW7 in tumor development and have identified a number of potential targets for therapeutic intervention.en
dc.language.isoen_USen
dc.publisherImpact Journals LLCen
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792592/pdf/en
dash.licenseLAAen_US
dc.subjectthymic lymphomaen
dc.subjectFBXW7en
dc.subjectmTORen
dc.subjectrapamycinen
dc.subjectradiationen
dc.titleExpression profiling reveals transcriptional regulation by Fbxw7/mTOR pathway in radiation-induced mouse thymic lymphomasen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalOncotargeten
dash.depositing.authorLiu, Yueyongen_US
dc.date.available2016-04-01T15:47:45Z
dash.contributor.affiliatedLiu, Yueyong


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