Down-Regulation of EBV-LMP1 Radio-Sensitizes Nasal Pharyngeal Carcinoma Cells via NF-κB Regulated ATM Expression 英文参考文献.docVIP

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Down-Regulation of EBV-LMP1 Radio-Sensitizes Nasal Pharyngeal Carcinoma Cells via NF-κB Regulated ATM Expression 英文参考文献.doc

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Down-Regulation of EBV-LMP1 Radio-Sensitizes Nasal Pharyngeal Carcinoma Cells via NF-κB Regulated ATM Expression 英文参考文献

Down-RegulationofEBV-LMP1Radio-SensitizesNasal PharyngealCarcinomaCellsviaNF-kBRegulatedATM Expression XiaoqianMa1.¤,LifangYang1,2.,LanboXiao1,MinTang1,LiyuLiu1,ZijianLi1,MengyaoDeng1 ,Lunquan Sun2,4*,YaCao1,3,4 * 1CancerResearchInstitute,XiangyaSchoolofMedicine,CentralSouthUniversity,Changsha,China,2CenterforMolecularMedicine,CentralSouthUniversity,Xiangya Hospital,Changsha,China,3KeyLaboratoryofCarcinogenesisandInvasion,MinistryofEducation,KeyLaboratoryofCarcinogenesis,MinistryofHealth,Changsha,China, 4CenterforMolecularImaging,CentralSouthUniversity,Changsha,China Abstract Background:Thelatentmembraneprotein1(LMP1)encodedbyEBVisexpressedinthemajorityofEBV-associatedhuman malignancies and has been suggested to be one of the major oncogenic factors in EBV-mediated carcinogenesis. In previousstudiesweexperimentallydemonstratedthatdown-regulationofLMP1expressionbyDNAzymescouldincrease radiosensitivitybothincellsandinaxenograftNPCmodelinmice. Results: In this study we explored the molecular mechanisms underlying the radiosensitization caused by the down- regulationofLMP1innasopharyngealcarcinoma.ItwasconfirmedthatLMP1couldup-regulateATMexpressioninNPCs. Bioinformatic analysis of the ATM ptomoter region revealed three tentative binding sites for NF-kB. By using a specific inhibitorofNF-kBsignalingandthedominantnegativemutantofIkappaB,itwasshownthattheATMexpressioninCNE1- LMP1cellscouldbeefficientlysuppressed.InhibitionofLMP1expressionbytheDNAzymeledtoattenuationoftheNF-kB DNAbinding activity.We furthershowedthat thesilenceofATMexpression byATM-targetedsiRNA couldenhance the radiosensitivityinLMP1positiveNPCcells. Conclusions:Together,ourresultsindicatethatATMexpressioncanberegulatedbyLMP1viatheNF-kBpathwaysthrough directpromoterbinding,whichresultedinthechangeofradiosensitivityinNPCs. Citation:MaX,YangL,XiaoL,TangM,LiuL,etal.(2011)Down-RegulationofEBV-LMP1Radio-SensitizesNasalPharyngealCarcinomaCellsviaNF-k BRegulated ATMExpression.PLoSONE6(11):e24647.doi:10.1371