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1、THEJOURNALOFBIOLOGICALCHEMISTRYVol.265,No.34,IssueofDecember5,pp.21172-21178,199O01990byTheAmericanSocietyforBiochemistryandMolecularBiology,Inc.PrintedinCJ.S.A.RoleofInsulin-likeGrowthFactorsandtheTypeIInsulin-likeGrowthFactorReceptorintheEstrogen-stimulatedProliferationofHumanBreastCanc
2、erCells*(Receivedforpublication,June4,1990)AlistairJ.Stewart*,MichaelD.Johnson,FelicityE.B.May&andBruceR.WestleyllFromtheUniversityDepartmentofPathology,RoyalVictoriaInfirmary,NewcastleuponTyneNE14LP,UnitedKingdomEstrogensensitizestheMCF-7estrogen-responsiveastransforminggrowthfactor(Y(TG
3、F-a)’(Dicksonetal.,breastcancercelllinetothemitogeniceffectofinsulin1986;Perroteauetal.,1986),transforminggrowthfactor/3andtheinsulin-likegrowthfactors(IGFs).Thissensi-(TGF-P)(Knabbeetal.,1987),andplatelet-derivedgrowthtizationisspecificforestrogenandoccursatphysio-factor(Bronzertetal.,19
4、87)aresynthesizedbybreastcancerlogicalconcentrationsofestradiol.Dose-responseex-cellsinculture.Further,somestudieshavesuggestedthattheperimentswithinsulin,IGF-I,andIGF-IIsuggestedsynthesisofTGF-(wisincreasedbyestrogens(Lippmanetal.,thatthesensitizationismediatedthroughthetypeI1987)whileth
5、esecretionofTGF-/?,anegativegrowthfactor,IGFreceptor.Bindingexperimentswith‘2SI-IGF-Iandisinhibited(Knabbeetal.,1987).hybridizationofatypeIIGFreceptorprobetoRNAConflictingresultshavebeenreportedfortheexpressionofDownloadedfromshowedthatthelevelsofthetypeIIGFreceptorandIGF-Iinbreasttumorce
6、lls.Initially,Huffetal.(1986anditsmRNAareincreased7-and6.5-fold,respectively,1988)reportedthatIGF-Iissynthesizedunderestrogencon-byestradiol.IGF-Iandestradiolhadsimilarsynergis-trolinMCF-7cells.However,KareyandSirbasku(1988)ticeffectsonotherestrogen-responsivebreastcancerusinganimmunoassa
7、ytomeasureIGF-Iinconditionedme-celllines,butIGF-IaloneincreasedtheproliferationdiumreportedthatMCF-7cellsdonotproducebiologicallyoftheMDAMB-231celllinewhichisnotresponsivesignificantconcentrationsofIGF-I,and,subsequently,Yeeetwww.jbc.orgtoestrogens.Theseexperimentss
