Caveolae Contribute to the Apoptosis Resistance Induced by the α1A-Adrenoceptor in Androgen-Independent Prostate Cancer Cells 英文参考文献.docVIP

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Caveolae Contribute to the Apoptosis Resistance Induced by the α1A-Adrenoceptor in Androgen-Independent Prostate Cancer Cells 英文参考文献.doc

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Caveolae Contribute to the Apoptosis Resistance Induced by the α1A-Adrenoceptor in Androgen-Independent Prostate Cancer Cells 英文参考文献

CaveolaeContributetotheApoptosisResistance Inducedbythea1A-AdrenoceptorinAndrogen- IndependentProstateCancerCells MariaKatsogiannou1,2,CharbelElBoustany1,2,FlorianGackiere1,2,PhilippeDelcourt1,2,AnneAthias3, PascalMariot1,2,EtienneDewailly1,2,NathalieJouy4,ChristopheLamaze5,6,GabrielBidaux1,2 ,Brigitte Mauroy1,2,NataliaPrevarskaya1,2,ChristianSlomianny1,2 * 1InsermU800,Universite′ Lille1SciencesetTechnologies,Villeneuved’Ascq,France,2LaboratoiredePhysiologieCellulaire,Universite′ Lille1SciencesetTechnologies, Villeneuved’Ascq,France,3Lipidomique-IFR100,Ho?pitalduBocage,Dijon,France,4IFR114,IMPRT,InstitutdeRecherchesurleCancerdeLille,Lille,France,5Institut Curie,CentredeRecherche,LaboratoireTrafic,SignalisationetCiblageIntracellulaires,Paris,France,6CNRS,UMR144,Paris,France Abstract Background: During androgen ablation prostate cancer cells’ growth and survival become independent of normal regulatory mechanisms. These androgen-independent cells acquire the remarkable ability to adapt to the surrounding microenvironment whose factors, such as neurotransmitters, influence their survival. Although findings are becoming evident about the expression of a1A-adrenoceptors in prostate cancer epithelial cells, their exact functional role in androgen-independent cells has yet to be established. Previous work has demonstrated that membrane lipid rafts associatedwithkeysignallingproteinsmediategrowthandsurvivalsignallingpathwaysinprostatecancercells. Methodology/Principal Findings: In order to analyze the membrane topology of the a1A-adrenoceptor we explored its presence by a biochemical approach in purified detergent resistant membrane fractions of the androgen-independent prostatecancercelllineDU145.Electronmicroscopyobservationsdemonstratedthecolocalisationofthea1A-adrenoceptor with caveolin-1, the major protein component of caveolae. In addition, we showed that agonist stimulation of the a1A- adrenoceptor induced resistance to thapsigargin-induced apoptosis and that