Differential Effect of Growth Factors on Invasion and Proliferation of Endocrine Resistant Breast Cancer Cells 英文参考文献.docVIP

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Differential Effect of Growth Factors on Invasion and Proliferation of Endocrine Resistant Breast Cancer Cells 英文参考文献.doc

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Differential Effect of Growth Factors on Invasion and Proliferation of Endocrine Resistant Breast Cancer Cells 英文参考文献

DifferentialEffectofGrowthFactorsonInvasionand ProliferationofEndocrineResistantBreastCancerCells MaithamA.Khajah1,SanaaAlSaleh2,PrincyM.Mathew1,YunusA.Luqmani1* 1FacultyofPharmacy,KuwaitUniversity,Safat,Kuwait,2FacultyofMedicine,KuwaitUniversity,Safat,Kuwait Abstract WehaveestablishedseveralbreastcancercelllinesthatexhibitapermanentER-depletedphenotype,inducedbyshRNA transfectionofMCF-7cells,whichaffordausefulmodelforstudyingacquiredendocrineresistance.Previouslyweshowed thatMDA-231aswellasER-silencedcellscouldinvadethroughsimulatedextracellularmatrixcomponents.However,the contribution of individualserum components responsible for cell invasion was not determined. In the present study, an under-agarose gel assay was used to quantitatively assess the invasive movement of two ER-silenced cell lines (pII and YS2.5)incomparisontotheparentalMCF-7,theERnegativeMDA-231,andnormalHBL100cells,aswellasalinethatwas ER-shRNAtransfectedbutfailedtoexhibitERdown-regulation(YS1.2).Wealsoexaminedtheeffectofthegrowthfactors EGF,IGF-1,TGFb,PDGFCandRANTESonpIIcellinvasionandproliferation.AllbreastcancercelllineswhichhadreducedER expressionexhibitedaserum-dependentinvasiveabilityrelatedtothedegreeofinducedERloss.TGFbtreatmentinhibited pII cell proliferation and enhanced their invasive ability but at a relatively high dose. IGF-1 and EGF enhanced pII cell proliferation,withthelatterplayingthemajorroleinpromotingcellinvasion.PDGFCdidnotaffecteitherprocessalthough it is highly expressed in pII cells. Differential effects were observed on activation of Akt and ERK1/2 suggesting their involvementasintracellularmediatorsofEGFinducedinvasion,inpartthroughtheregulationofmatrixmetalloproteinase activity. Targeting EGF receptor tyrosine kinase activity by erlotinib resulted in significant inhibition of both pII cell proliferation and directional invasion towards EGF suggesting that this drug has potential therapeutic usefulness for preventingspreadofparticularlyendocrineresistantbreastcancer. C