Cdx1 and c-Myc Foster the Initiation of Transdifferentiation of the Normal Esophageal Squamous Epithelium toward Barretts Esophagus 英文参考文献.docVIP

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Cdx1 and c-Myc Foster the Initiation of Transdifferentiation of the Normal Esophageal Squamous Epithelium toward Barretts Esophagus 英文参考文献.doc

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Cdx1 and c-Myc Foster the Initiation of Transdifferentiation of the Normal Esophageal Squamous Epithelium toward Barretts Esophagus 英文参考文献

Cdx1andc-MycFostertheInitiationof TransdifferentiationoftheNormalEsophageal SquamousEpitheliumtowardBarrett’sEsophagus DouglasB.Stairs1,2,HiroshiNakagawa1,2,AndresKlein-Szanto4,ShukriyyahD.Mitchell1,2,DebraG. Silberg1,2,JohnW.Tobias3,JohnP.Lynch1,2,AnilK.Rustgi1,2 * 1Division of Gastroenterology, Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 2DivisionofGastroenterology,DepartmentofGenetics,AbramsonCancerCenter,UniversityofPennsylvania,Philadelphia,Pennsylvania,UnitedStatesofAmerica,3Penn CenterforBioinformatics,UniversityofPennsylvania,Philadelphia,Pennsylvania,UnitedStatesofAmerica,4FoxChaseCancerCenter,Philadelphia,Pennsylvania,United StatesofAmerica Abstract Background: Barrett’s esophagus is a premalignant condition whereby the normal stratified squamous esophageal epithelium undergoes a transdifferentiation program resulting in a simple columnar epithelium reminiscent of the small intestine.Thesechangesaretypicallyassociatedwiththestratifiedsquamousepitheliumchronicallyexposedtoacidand bilesaltsasaresultofgastroesophagealrefluxdisease(GERD).Despitethiswell-definedepidemiologicassociationbetween acid reflux and Barrett’s esophagus, the genetic changes that induce this transdifferentiation process in esophageal keratinocyteshaveremainedundefined. Methodology/PrincipalFindings:TobegintoidentifythegeneticchangesresponsiblefortransdifferentiaitoninBarrett’s esophagus, we performed a microarray analysis of normal esophageal, Barrett’s esophagus and small intestinal biopsy specimenstoidentifycandidatesignalingpathwaysandtranscriptionfactorsthatmaybeinvolved.Throughthisscreenwe identifiedtheCdx1homeodomaintranscriptionfactorandthec-mycpathwayaspossiblecandidates.Cdx1andc-mycwere then tested for their ability to induce transdifferentiation in immortalized human esophageal keratinocytes using organotypic culturing methods. Analyses of these cultures reveal that c-myc and cdx1 cooperate