EpigeneticInformationandEstrogenReceptorAlphaExpressioninBreastCancer医学论文

Epigenetic Information and Estrogen Receptor Alpha Expression in Breast Cancer_ҽѧÂÛÎÄ ×÷ÕߣºLaura

EpigeneticInformationandEstrogenReceptorAlphaExpressioninBreast Cancer_ҽѧÂÛÎÄ ×÷ÕߣºLauraGiacintia,b,PierPaoloClaudioa,MassimoLopezb,Antonio Giordanoa,c ¡¾¹Ø¼ü´Ê¡¿ Breast,cancer,•,Gene,expression,regulation,•,Estrogen,receptors,&#82 26;,Anticancer,drug,combinations ¡¡¡¡LEARNINGOBJECTIVES ¡¡¡¡Aftercompletingthiscourse,thereaderwillbeableto: Describetheroleofepigeneticinformationintheregulationofgeneexpressionandin thedevelopmentofcancer. ¡¡¡¡Explaintheimportantroleofestrogenreceptorexpressioninbreastcancerasa prognosticmarkerandpredictivefactorofresponsetoendocrinetherapy. ¡¡¡¡Evaluatethecurrentandpotentialrolethatthecomprehensionofthemolecular biologyofatumormayhaveinfindinganewtherapeuticapproachincancer treatment. ¡¡¡¡TheCMEactivityforthisarticleisforthcoming. ¡¡¡¡ABSTRACT ¡¡¡¡Inindustrializedcountries,breastcanceristhemostcommontumorinwomen. Thetumorexpressionofestrogenreceptors(ERs)isaveryimportantmarkerfor prognosisandamarkerthatispredictiveofresponsetoendocrinetherapy.Thelossof ERexpressionportendsapoorprognosisand,inasignificantfractionofbreast cancers,thisrepressionisaresultofthehypermethylationofCpGislandswithinthe ER-promoter.Hypermethylationisoneofthebestknownepigeneticeventsin mammaliancells.Overthelastfewyears,manystudieshavefoundthatother epigeneticevents,suchasdeacetylationandmethylationofhistones,areinvolvedin thecomplexmechanismthatregulatespromotertranscription.Theexactinterplayof thesefactorsintranscriptionalrepressionactivityisnotyetwellunderstood. Inhibitorsofsomeofthesearecurrentlybeingstudiedasnewdrugsabletorestore ER-proteinexpressioninER-negativebreastcancercellsandtopromoteapoptosis anddifferentiation.Demethylatingagentsandhistonedeacetylase(HDAC)inhibitors arecandidatesforbecomingpotentnewdrugsincancertherapy.Thispaperreviews thecurrentunderstandingoftheroleofepigeneticinformationinthedevelopmentof canceranditssignificanceinbreastcanceraspredictivemarkersofERstatusandas newtargetsofanticancertherapy. ¡¡¡¡INTRODUCTION ¡¡¡¡Inindustrializedcountries,breastcanceristhemostcommontumorinwomen, anditisthemostimportantcauseofcancer-associatedmorbidityandmortality. Thankstoearlydiagnosisandthediscoveryofnewdrugs,cancer-associatedmortality