Silencing of Glutathione Peroxidase 3 through DNA Hypermethylation Is Associated with Lymph Node Metastasis in Gastric Carcinomas 英文参考文献.docVIP

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Silencing of Glutathione Peroxidase 3 through DNA Hypermethylation Is Associated with Lymph Node Metastasis in Gastric Carcinomas 英文参考文献.doc

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Silencing of Glutathione Peroxidase 3 through DNA Hypermethylation Is Associated with Lymph Node Metastasis in Gastric Carcinomas 英文参考文献

SilencingofGlutathionePeroxidase3throughDNA HypermethylationIsAssociatedwithLymphNode MetastasisinGastricCarcinomas Dun-FaPeng1,Tian-LingHu1,BarbaraG.Schneider2,ZhengChen1,5,Ze-KuanXu5,6,WaelEl-Rifai1,3,4 * 1DepartmentofSurgery,VanderbiltUniversityMedicalCenter,Nashville,Tennessee,UnitedStatesofAmerica,2DepartmentofMedicine,VanderbiltUniversityMedical Center, Nashville, Tennessee, United States of America, 3Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America,4DepartmentofVeteransAffairsTennesseeValleyHealthcareSystem,Nashville,Tennessee,UnitedStatesofAmerica,5DepartmentofGeneralSurgery,theFirst AffiliatedHospitalofNanjingMedicalUniversity,Nanjing,China,6InstituteofTumorBiology,JiangsuProvinceAcademyofClinicalMedicine,Nanjing,China Abstract Gastriccancerremainsthesecondleadingcauseofcancer-relateddeathintheworld.H.pyloriinfection,amajorriskfactor forgastriccancer,generateshighlevelsofreactiveoxygenspecies(ROS).Glutathioneperoxidase3(GPX3),aplasmaGPX member and a major scavenger of ROS, catalyzes the reduction of hydrogen peroxide and lipid peroxides by reduced glutathione.TostudytheexpressionandgeneregulationofGPX3,weexaminedGPX3geneexpressionin9gastriccancer celllines,108primarygastriccancersamplesand45normalgastricmucosaadjacenttocancersusingquantitativereal-time RT-PCR.DownregulationorsilencingofGPX3wasdetectedin8of9cancercelllines,83%(90/108)gastriccancerssamples, ascomparedtonon-tumoradjacentnormalgastricsamples(P,0.0001).ExaminationofGPX3promoterdemonstratedDNA hypermethylation($10%methylationleveldeterminedbyBisulfitePyrosequencing)in6of9cancercelllinesand60%of gastric cancer samples (P=0.007). We also detected a significant loss of DNA copy number of GPX3 in gastric cancers (P,0.001). Treatment of SNU1 and MKN28 cells with 5-Aza-29 Deoxycytidine restored the GPX3 gene expression with a significantdemethylationofGPX3promoter.ThedownregulationofGPX3expressionandGPX3promoterhypermethyla- tionweresi