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c-Myc and Transforming Growth Factor α Enhance the Development of Hepatic Lesions Due to Mutant β-Catenin in Transgenic Mice

机译:c-Myc和转化生长因子α增强因突变体-Catenin引起的肝病变在转基因小鼠中的发展

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AlterationsintheWntsignalingpathwayareassociatedwithdiversecancers,includinghepatocellularcarcinoma(HCC).ThedevelopmentofHCCisthoughttobeamultistageprocessinwhichmultiplegeneticalterationsarenecessary.FewstudieshaveassessedtheeffectofaberrantWntsignalingactivityinassociationwithothermolecularalterationsinHCC.Herewesoughttodeterminewhetherco-overexpressionofc-MycorTGF#945;,2signalingmoleculesknowntocontributetoHCCdevelopment,enhancedthedevelopmentofhepaticlesionsassociatedwithastabilized#946;-catenin.Thecoexpressionofmutant#946;-cateninwitheitherc-MycorTGF#945;withinhepatocytesincreasedtheseverityofhepaticlesionscomparedwiththatassociatedwithanyofthetransgenesexpressedindividually.Thecoexpressionofmutant#946;-cateninwithc-MycorTGF#945;resultedinseverehepatomegalynecessitatingtheeuthanasiaofmicebyanaverageof156and128d,respectively,afterthecessationofdoxycycline.Theexpressionofmutant#946;-cateninaloneresultedinmildtomoderatehepatomegalythatpromptedtheeuthanasiaofmicebyanaverageof75dafterthecessationofdoxycycline.Collectively,thesefindingsindicatethatcoexpressionofc-MycorTGF#945;delaystheonsetofendstagehepaticdiseaseyetenhancestheseverityofhepaticlesionsduetomutant#946;-catenin.
机译:AlterationsintheWntsignalingpathwayareassociatedwithdiversecancers,includinghepatocellularcarcinoma(HCC).ThedevelopmentofHCCisthoughttobeamultistageprocessinwhichmultiplegeneticalterationsarenecessary.FewstudieshaveassessedtheeffectofaberrantWntsignalingactivityinassociationwithothermolecularalterationsinHCC.Herewesoughttodeterminewhetherco-overexpressionofc-MycorTGF#945;,2signalingmoleculesknowntocontributetoHCCdevelopment,enhancedthedevelopmentofhepaticlesionsassociatedwithastabilized#946;#-catenin.Thecoexpressionofmutant 946; -cateninwitheitherc-MycorTGF#945;#withinhepatocytesincreasedtheseverityofhepaticlesionscomparedwiththatassociatedwithanyofthetransgenesexpressedindividually.Thecoexpressionofmutant 946; -cateninwithc-MycorTGF #945;在强力霉素停止后,在巨大的巨大肝中分别使米氏平均安乐死达到156和128d。突变体#946;的表达导致轻度中度肝肿大,促使提示的米黄色平均安乐死75天后。这些发现共同表明,c-MycorTGF#945的共表达;延迟了肝病末期眼病的发作,从而增强了肝突变的严重性,因为突变#946; -catenin。

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