MUC1 Contributes to BPDE-Induced Human Bronchial Epithelial Cell Transformation through Facilitating EGFR Activation 英文参考文献.docVIP

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MUC1 Contributes to BPDE-Induced Human Bronchial Epithelial Cell Transformation through Facilitating EGFR Activation 英文参考文献.doc

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MUC1 Contributes to BPDE-Induced Human Bronchial Epithelial Cell Transformation through Facilitating EGFR Activation 英文参考文献

MUC1ContributestoBPDE-InducedHumanBronchial EpithelialCellTransformationthroughFacilitatingEGFR Activation XiulingXu1.,LangBai1.,WenshuChen1,MabelT.Padilla1,YushiLiu1,KwangChulKim2, StevenA.Belinsky1,YongLin1* 1MolecularBiologyandLungCancerProgram,LovelaceRespiratoryResearchInstitute,Albuquerque,NewMexico,UnitedStatesofAmerica,2DepartmentofPhysiology andLungCenter,TempleUniversitySchoolofMedicine,Philadelphia,Pennsylvania,UnitedStatesofAmerica Abstract Althoughitis well knownthatepidermal growthfactor receptor (EGFR) is involvedin lung cancer progression, whether EGFR contributes to lung epithelial cell transformation is less clear. Mucin 1 (MUC1 in human and Muc1 in animals), a glycoproteincomponentofairwaymucus,isoverexpressedinlungtumors;however,itsroleandunderlyingmechanismsin earlystagelungcarcinogenesisisstillelusive.ThisstudyprovidesstrongevidencedemonstratingthatEGFRandMUC1are involvedinbronchialepithelialcelltransformation.KnockdownofMUC1expressionsignificantlyreducedtransformationof immortalized human bronchial epithelial cells induced by benzo[a]pyrene diol epoxide (BPDE), the active form of the cigarettesmoke(CS)carcinogenbenzo(a)pyrene(BaP)s.BPDEexposurerobustlyactivatedapathwayconsistingofEGFR, AktandERK,andblockingthispathwaysignificantlyincreasedBPDE-inducedcelldeathandinhibitedcelltransformation. SuppressionofMUC1expressionresultedinEGFRdestabilizationandinhibitionoftheBPDE-inducedactivationofAktand ERKandincreaseofcytotoxicity.TheseresultsstronglysuggestanimportantroleforEGFRinBPDE-inducedtransformation, andsubstantiatethatMUC1isinvolvedinlungcancerdevelopment,atleastpartlythroughmediatingcarcinogen-induced activationoftheEGFR-mediatedcellsurvivalpathwaythatfacilitatescelltransformation. Citation: Xu X, Bai L, Chen W, Padilla MT, Liu Y, et al. (2012) MUC1 Contributes to BPDE-Induced Human Bronchial Epithelial Cell Transformation through FacilitatingEGFRActivation.PLoSONE7(3):e33846.doi:10.1371/journal.pone.0033846 Editor:Shi-YongSun,EmoryUnivers