项目来源

德国科学基金(DFG)

项目主持人

PatrickMichl；

项目受资助机构

UniversitätsklinikumHalleAöR,DepartmentfürInnereMedizin,UniversitätsklinikundPoliklinikfürInnereMedizinI

项目编号

267164735

立项年度

2014

立项时间

未公开

项目级别

国家级

研究期限

未知 / 未知

受资助金额

未知

学科

Gastroenterology

学科代码

未公开

基金类别

ResearchGrants

关键词

未公开

参与者

ProfessorDr.PatrickMichl

参与机构

未公开

项目标书摘要：Previously,weidentifiedthetranscriptionfactorCUX1asimportantmediatoroftumorprogression,metastasisandresistancetoapoptosisinpancreaticcancer.Furthermore,wecharacterizedseveralCUX1targetgenesmodulatingitseffectsoninvasionandsurvival.WecouldshowthatupregulationofCUX1bysurvivalpathwaysleadstoenhancedresistanceagainstchemotherapeuticdrugs.ThisprojectaimstoinvestigatetheeffectofCux1oncarcinogenesis,tumorprogressionanddrugresistanceinvivobycharacterizationofaconditionalknock-inmousemodelofCux1whichwegeneratedrecently.Thismousemodelwillbecrossedwithestablishedconditionalmousemodelsofpancreaticprecursorlesions(LSL-KrasG12D;Pdx1-Cre;KC-mouse)andinvasivepancreaticcancer(LSL-KrasG12D;LSL-p53R172H;Pdx1-Cre;KPC-mouse).TheprojectwillexamineifCux1inthecontextofactivatedK-Rasleadstothedevelopmentofinvasivecancersorisabletoenhancetumorprogression.Inaddition,wewillinvestigatetheimpactofCux1onresistancetodrug-inducedapoptosisaftertreatmentwithchemotherapeuticdrugssuchasgemcitabine.Byusinggenome-widetranscriptomeprofiling,Cux1-dependenttargetgenesmodulatingcelldifferentiation,tumorigenesisandprogressionwillbeidentifiedandindividuallycharacterized.

Application Abstract: Previously,weidentifiedthetranscriptionfactorCUX1asimportantmediatoroftumorprogression,metastasisandresistancetoapoptosisinpancreaticcancer.Furthermore,wecharacterizedseveralCUX1targetgenesmodulatingitseffectsoninvasionandsurvival.WecouldshowthatupregulationofCUX1bysurvivalpathwaysleadstoenhancedresistanceagainstchemotherapeuticdrugs.ThisprojectaimstoinvestigatetheeffectofCux1oncarcinogenesis,tumorprogressionanddrugresistanceinvivobycharacterizationofaconditionalknock-inmousemodelofCux1whichwegeneratedrecently.Thismousemodelwillbecrossedwithestablishedconditionalmousemodelsofpancreaticprecursorlesions(LSL-KrasG12D;Pdx1-Cre;KC-mouse)andinvasivepancreaticcancer(LSL-KrasG12D;LSL-p53R172H;Pdx1-Cre;KPC-mouse).TheprojectwillexamineifCux1inthecontextofactivatedK-Rasleadstothedevelopmentofinvasivecancersorisabletoenhancetumorprogression.Inaddition,wewillinvestigatetheimpactofCux1onresistancetodrug-inducedapoptosisaftertreatmentwithchemotherapeuticdrugssuchasgemcitabine.Byusinggenome-widetranscriptomeprofiling,Cux1-dependenttargetgenesmodulatingcelldifferentiation,tumorigenesisandprogressionwillbeidentifiedandindividuallycharacterized.