Retinoic Acid Mediates Regulation of Network Formation by COUP-TFII and VE-Cadherin Expression by TGFβ Receptor Kinase in Breast Cancer Cells 英文参考文献.docVIP

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Retinoic Acid Mediates Regulation of Network Formation by COUP-TFII and VE-Cadherin Expression by TGFβ Receptor Kinase in Breast Cancer Cells 英文参考文献.doc

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Retinoic Acid Mediates Regulation of Network Formation by COUP-TFII and VE-Cadherin Expression by TGFβ Receptor Kinase in Breast Cancer Cells 英文参考文献

RetinoicAcidMediatesRegulationofNetworkFormation byCOUP-TFIIandVE-CadherinExpressionbyTGFb ReceptorKinaseinBreastCancerCells PriyaPrahalad,SivanesanDakshanamurthy,HabtomRessom,StephenW.Byers* LombardiComprehensiveCancerCenter,DepartmentofOncology,GeorgetownUniversity,Washington,D.C.,UnitedStatesofAmerica Abstract Tumordevelopment,growth,andmetastasisdependontheprovisionofanadequatevascularsupply.Thiscanbedueto regulated angiogenesis, recruitment of circulating endothelial progenitors, and/or vascular transdifferentiation. Our previousstudiesshowedthatretinoicacid(RA)treatmentconvertsasubsetofbreastcancercellsintocellswithsignificant endothelial genotypic and phenotypic elements including marked induction of VE-cadherin, which was responsible for somebutnotallmorphologicalchanges.Thepresentstudydemonstratesthatoftheendothelial-relatedgenesinducedby RA treatment, only a few were affected by knockdown of VE-cadherin, ruling it out as a regulator of the RA-induced endothelial genotypic switch. In contrast, knockdown of the RA-induced gene COUP-TFII prevented the formation of networksinMatrigelbuthadnoeffectonVE-cadherininductionorcellfusion.Twopan-kinaseinhibitorsmarkedlyblocked RA-inducedVE-cadherinexpressionandcellfusion.However,RAtreatmentresultedinamarkedandbroadreductionin tyrosine kinaseactivity. Severalgenesin the TGFb signaling pathwaywere inducedby RA, and specific inhibitionof the TGFbtypeIreceptorblockedbothRA-inducedVE-cadherinexpressionandcellfusion.Togetherthesedataindicatearole fortheTGFbpathwayandCOUP-TFIIinmediatingtheendothelialtransdifferentiatingpropertiesofRA. Citation:PrahaladP,DakshanamurthyS,RessomH,ByersSW(2010)RetinoicAcidMediatesRegulationofNetworkFormationbyCOUP-TFIIandVE-Cadherin ExpressionbyTGFbReceptorKinaseinBreastCancerCells.PLoSONE5(4):e10023.doi:10.1371/journal.pone.0010023 Editor:ErikH.J.Danen,LeidenUniversity,Netherlands ReceivedOctober20,2009;AcceptedMarch11,2010;PublishedApril6,2010 Copyright: ? 2010 Prahalad et al. This is an o