摘要
Objective:Theelevatedincidenceofobesityhasbeenparalleledwithhigherrisksofbreastcancer.Highadiposityincreasesleptinsecretionfromadiposetissue,whichinturnincreasescancercellproliferation.Theinterplaybetweenleptinandestrogenisoneofthemechanismsthroughwhichleptininfluencesbreastcarcinogenesis.Anunbalancedestrogenmetabolismincreasestheformationsofcatecholestrogenquinones,DNAadducts,andcancermutations.ThisstudyaimstoinvestigatetheeffectofleptinonsomeestrogenmetabolicenzymesandDNAadductioninbreastcancercells.Methods:Highperformanceliquidchromatography(HPLC)wasperformedtoanalyzetheDNAadducts4-OHE1[E2]-1-N3adenineand4-OHE1[E2]-1-N7guanine.Reportergeneassay,realtimereversetranscriptionpolymerasechainreaction(realtimeRT-PCR),andWesternblotwereusedtoassesstheexpressionofestrogenmetabolizinggenesandenzymes:CytochromeP-4501B1(CYP1B1),Nicotinamideadeninedinucleotidephosphate-quinoneoxidoreductase1(NQO1),andCatechol-O-methyltransferase(COMT).Results:LeptinsignificantlyincreasedtheDNAadducts4-OHE1[E2]-1-N3adenineand4-OHE1[E2]-1-N7guanine.Furthermore,leptinsignificantlyupregulatedCYP1B1promoteractivityandproteinexpression.TheluciferasepromoteractivitiesofNQO1andmRNAlevelsweresignificantlyreduced.Moreover,leptingreatlyreducedthereporteractivitiesoftheCOMT-P1andCOMT-P2promotersanddiminishedtheproteinexpressionofCOMT.Conclusions:LeptinincreasesDNAadductlevelsinbreastcancercellspartlybyaffectingkeygenesandenzymesinvolvedinestrogenmetabolism.Thus,increasedfocusshouldbedirectedtowardleptinanditseffectsontheestrogenmetabolicpathwayasaneffectiveapproachagainstbreastcancer.
出版日期
2016年04月14日（中国期刊网平台首次上网日期，不代表论文的发表时间）
