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1、TheAAPSJournal,Vol.17,No.1,January2015(#2014)DOI:10.1208/s12248-014-9668-6ReviewArticleRoleoftheBreastCancerResistanceProtein(BCRP/ABCG2)inDrugTransport—anUpdate1,21QingchengMaoandJashvantD.UnadkatReceived20July2014;accepted3September2014;publishedonline19September2014Abstract.Thehumanbreastcancerr
2、esistanceprotein(BCRP,genesymbolABCG2)isanATP-bindingcassette(ABC)effluxtransporter.Itwassonamedbecauseitwasinitiallyclonedfromamultidrug-resistantbreastcancercelllinewhereitwasfoundtoconferresistancetochemotherapeuticagentssuchasmitoxantroneandtopotecan.Sinceitsdiscoveryin1998,thesubstratesofBCRPha
3、vebeenrapidlyexpandingtoincludenotonlytherapeuticagentsbutalsophysiologicalsubstancessuchasestrone-3-sulfate,17β-estradiol17-(β-D-glucuronide)anduricacid.Likewise,atleasthundredsofBCRPinhibitorshavebeenidentified.Amongnormalhumantissues,BCRPishighlyexpressedontheapicalmembranesoftheplacentalsyncytio
4、trophoblasts,theintestinalepithelium,theliverhepatocytes,theendothelialcellsofbrainmicrovessels,andtherenalproximaltubularcells,contributingtotheabsorption,distribution,andeliminationofdrugsandendogenouscompoundsaswellastissueprotectionagainstxenobioticexposure.Asaresult,BCRPhasnowbeenrecognizedbyt
5、heFDAtobeoneofthekeydrugtransportersinvolvedinclinicallyrelevantdrugdisposition.Wepublishedahighly-accessedreviewarticleonBCRPin2005,andmuchprogresshasbeenmadesincethen.Inthisreview,weprovideanupdateofcurrentknowledgeonbasicbiochemistryandpharmacologicalfunctionsofBCRPaswellasitsrelevancetodrugresi
6、stanceanddrugdisposition.KEYWORDS:ABCG2;ATP-bindingcassette;BCRP;drugtransport;transporter.INTRODUCTIONpresentreview,wewillprovideanupdateofcurrentThehumanATP-bindingcassette(ABC)proteinsbelongknowledgeonthistopic.toalargeproteinsuperfamilythatnowcomprises48members(http://nutrigene.4t.com/humanabc.
7、htm).ManyofBCRPINHUMANCANCERSthehumanABCproteinsareeffluxtransporters,andthreeofthem,namelyP-glycoprotein(P-gp,genesymbolABCB1),Themajorityoftheworkinthisareahasbeendonewiththemultidrugresistanceprotein1(MRP
