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Retinoid Signaling in Pancreatic Cancer, Injury and Regeneration 英文参考文献
RetinoidSignalinginPancreaticCancer,Injuryand
Regeneration
EmilyK.Colvin1,JohanaM.Susanto1,JamesG.Kench1,2,ViviennaN.Ong1,AmandaMawson1 ,Mark
Pinese1,DavidK.Chang1,3,IlseRooman1,SandraA.O’Toole1,2,4,DavendraSegara1,ElizabethA.
Musgrove1,RobertL.Sutherland1,4,MinotiV.Apte4,5,ChristopherJ.Scarlett1,6,AndrewV.Biankin1,3,4
*
1Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia, 2Department of Tissue Pathology and Diagnostic Oncology, Royal
PrinceAlfredHospital,CentralClinicalSchool,UniversityofSydney,Camperdown,Australia,3DivisionofSurgery,BankstownHospital,EldridgeRoad,Bankstown,Sydney,
Australia,4StVincent’sClinicalSchool,FacultyofMedicine,TheUniversityofNewSouthWales,Australia,5PancreaticResearchGroup,SouthWesternSydneyClinical
School, School of Medical Sciences, The University of New South Wales, Australia, 6School of Environmental and Life Sciences, University of Newcastle, Ourimbah,
Australia
Abstract
Background:Activationofembryonicsignalingpathwaysquiescentintheadultpancreasisafeatureofpancreaticcancer
(PC).ThesediscoverieshaveledtothedevelopmentofnovelinhibitorsofpathwayssuchasNotchandHedgehogsignaling
thatarecurrentlyinearlyphaseclinicaltrialsinthetreatmentofseveralcancertypes.Retinoidsignalingisalsoessentialfor
pancreatic development, and retinoid therapy is used successfully in other malignancies such as leukemia, but little is
knownconcerningretinoidsignalinginPC.
Methodology/Principal Findings: We investigated the role of retinoid signaling in vitro and in vivo in normal pancreas,
pancreatic injury, regeneration and cancer. Retinoid signaling is active in occasional cells in the adult pancreas but is
markedlyaugmentedthroughouttheparenchymaduringinjuryandregeneration.Bothchemicallyinducedandgenetically
engineered mouse models of PC exhibit a lack of retinoid signaling activity compared to normal pancreas. As a
consequence,weinvestigatedCellularRetinoidBindingProtein1(CRBP1),akeyregulatorofretinoidsignalingknownt
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