000172308 001__ 172308
000172308 005__ 20180317092727.0
000172308 0247_ $$2doi$$a10.1073/pnas.1012705107
000172308 02470 $$2ISI$$a000282512000041
000172308 037__ $$aARTICLE
000172308 245__ $$aPolymorphic genetic control of tumor invasion in a mouse model of pancreatic neuroendocrine carcinogenesis
000172308 269__ $$a2010
000172308 260__ $$c2010
000172308 336__ $$aJournal Articles
000172308 520__ $$aCancer is a disease subject to both genetic and environmental influences. In this study, we used the RIP1-Tag2 (RT2) mouse model of islet cell carcinogenesis to identify a genetic locus that influences tumor progression to an invasive growth state. RT2 mice inbred into the C57BL/6 (B6) background develop both non-invasive pancreatic neuroendocrine tumors (PNET) and invasive carcinomas with varying degrees of aggressiveness. In contrast, RT2 mice inbred into the C3HeB/Fe (C3H) background are comparatively resistant to the development of invasive tumors, as are RT2 C3HB6(F1) hybrid mice. Using linkage analysis, we identified a 13-Mb locus on mouse chromosome 17 with significant linkage to the development of highly invasive PNETs. A gene residing in this locus, the anaplastic lymphoma kinase (Alk), was expressed at significantly lower levels in PNETs from invasion-resistant C3H mice compared with invasion-susceptible B6 mice, and pharmacological inhibition of Alk led to reduced tumor invasiveness in RT2 B6 mice. Collectively, our results demonstrate that tumor invasion is subject to polymorphic genetic control and identify Alk as a genetic modifier of invasive tumor growth.
000172308 6531_ $$aanaplastic lymphoma kinase
000172308 6531_ $$acancer modifier genes
000172308 6531_ $$amalignant progression
000172308 6531_ $$apancreas cancer
000172308 6531_ $$atransgenic mouse
000172308 6531_ $$aAnaplastic Lymphoma Kinase
000172308 6531_ $$aCancer Susceptibility Loci
000172308 6531_ $$aGenome-Wide Association
000172308 6531_ $$aCell Carcinomas
000172308 6531_ $$aTransgenic Mice
000172308 6531_ $$aAlk
000172308 6531_ $$aIdentification
000172308 6531_ $$aTumorigenesis
000172308 6531_ $$aMetastasis
000172308 6531_ $$aReceptor
000172308 700__ $$aChun, Matthew G. H.
000172308 700__ $$aMao, Jian-Hua
000172308 700__ $$aChiu, Christopher W.
000172308 700__ $$aBalmain, Allan
000172308 700__ $$0244728$$aHanahan, Douglas$$g192826
000172308 773__ $$j107$$k40$$q17268-17273$$tProceedings Of The National Academy Of Sciences Of The United States Of America
000172308 909CO $$ooai:infoscience.tind.io:172308$$particle$$pSV
000172308 909C0 $$0252335$$pCMSO$$xU12095
000172308 917Z8 $$x182396
000172308 937__ $$aEPFL-ARTICLE-172308
000172308 973__ $$aOTHER$$rREVIEWED$$sPUBLISHED
000172308 980__ $$aARTICLE