FOXM1 Upregulation Is an Early Event in Human Squamous Cell Carcinoma and it Is Enhanced by Nicotine during Malignant Transformation 英文参考文献.docVIP

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FOXM1 Upregulation Is an Early Event in Human Squamous Cell Carcinoma and it Is Enhanced by Nicotine during Malignant Transformation 英文参考文献.doc

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FOXM1 Upregulation Is an Early Event in Human Squamous Cell Carcinoma and it Is Enhanced by Nicotine during Malignant Transformation 英文参考文献

FOXM1UpregulationIsanEarlyEventinHuman SquamousCellCarcinomaanditIsEnhancedbyNicotine duringMalignantTransformation EmiliosGemenetzidis1,AmritaBose1,AdeelM.Riaz1,TracyChaplin2,BryanD.Young2,MuhammadAli1, DavidSugden3,JohannaK.Thurlow4,Sok-ChingCheong5,Soo-HwangTeo5,HongWan1 ,Ahmad Waseem1,EricK.Parkinson1,FaridaFortune1,Muy-TeckTeh1* 1CentreforClinicalandDiagnosticOralSciences,InstituteofDentistry,BartsTheLondonSchoolofMedicineandDentistry,QueenMaryUniversityofLondon,London, UnitedKingdom,2CancerResearchUKMedicalOncologyLaboratory,InstituteofDentistry,BartsTheLondonSchoolofMedicineandDentistry,QueenMaryUniversity ofLondon,London,UnitedKingdom,3DivisionofReproductionandEndocrinology,SchoolofBiomedicalandHealthSciences,King’sCollegeLondon,London,United Kingdom,4TheBeatsonInstituteforCancerResearch,Glasgow,UnitedKingdom,5CancerResearchInitiativesFoundation(CARIF),2ndFloorOutpatientCentre,Subang JayaMedicalCentre,Selangor,Malaysia Abstract Background: Cancerassociated withsmokinganddrinkingremainsaserioushealthproblemworldwide.Thesurvival of patientsisverypoorduetothelackofeffectiveearlybiomarkers.FOXM1overexpressionislinkedtothemajorityofhuman cancersbutitsmechanismremainsunclearinheadandnecksquamouscellcarcinoma(HNSCC). Methodology/Principal Findings:FOXM1mRNAandproteinexpressionswereinvestigatedin fourindependentcohorts (total75patients)consistingofnormal,premalignantandHNSCCtissuesandcellsusingquantitativePCR(qPCR),expression microarray,immunohistochemistryandimmunocytochemistry.EffectofputativeoralcarcinogensonFOXM1transcriptional activity was dose-dependently assayed and confirmed using a FOXM1-specific luciferase reporter system, qPCR, immunoblottingandshort-hairpinRNAinterference.Genome-widesinglenucleotidepolymorphism(SNP)arraywasused to‘trace’thegenomicinstabilitysignaturepatternin8clonallinesofFOXM1-inducedmalignanthumanoralkeratinocytes. Furthermore,acuteFOXM1upregulationinprimaryoralkeratinocytesdirectlyinducedgenomicinstability.Wehaveshown for