Protein Secretion Is Required for Pregnancy-Associated Plasma Protein-A to Promote Lung Cancer Growth In Vivo 英文参考文献.docVIP

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Protein Secretion Is Required for Pregnancy-Associated Plasma Protein-A to Promote Lung Cancer Growth In Vivo 英文参考文献.doc

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Protein Secretion Is Required for Pregnancy-Associated Plasma Protein-A to Promote Lung Cancer Growth In Vivo 英文参考文献

ProteinSecretionIsRequiredforPregnancy-Associated PlasmaProtein-AtoPromoteLungCancerGrowthIn Vivo HongPan1,3,SayakaHanada1,JunZhao1,4,LiMao1,2,MarkZhi-QingMa1* 1DepartmentofOncologyandDiagnosticSciences,UniversityofMarylandSchoolofDentistry,Baltimore,Maryland,UnitedStatesofAmerica,2ExperimentalTherapeutic Program,GreenbaumCancerCenter,UniversityofMaryland,Baltimore,Maryland,UnitedStatesofAmerica,3ThoracicSurgeryDepartment,AffiliatedTumorHospitalof GuangxiUniversity,Nanning,GuangxiProvince,People’sRepublicofChina,4DepartmentofThoracicMedicalOncology,PekingUniversitySchoolofOncology,Beijing CancerHospital,BeijingCancerInstituteforCancerResearch,HaidianDistrict,Beijing,People’sRepublicofChina Abstract Pregnancy-associatedplasmaprotein-A(PAPPA)hasbeenreportedtoregulatetheactivityofinsulin-likegrowthfactor(IGF) signalpathwaythroughproteolyticdegradationofIGFbindingproteins(IGFBPs)therebyincreasingthelocalconcentration offreeIGFsavailabletoreceptors.InthisstudywefoundthatPAPPAissecretedfromtwooutofsevenlungcancercelllines examined. None of immortalized normal bronchial epithelial cells (HBE) tested secrets PAPPA. There is no correlation between expression level and secretion of PAPPA in these cells. A cell line over-expressing PAPPA accompanied with secretion shows no notable changes in proliferation under cell culture conditions in vitro, but displays significantly augmentationoftumorgrowthinvivoinaxenograftmodel.Incontrast,acelllineover-expressingPAPPAwithoutsecretion exhibitsreductionoftumorgrowthbothinvitroandinvivo.Down-regulationofPAPPAexpressionandsecretionbyRNAi knockdown decreases tumor growth after implanted in vivo. The tumor promoting activity of PAPPA appears to be mediatedmainlythroughaugmentationoftheIGFsignalingpathwayasindicatedbynotableincreasesindownstreamAkt kinase phosphorylation in tumor samples. Our results indicate that PAPPA secretion may play an important role in lung cancergrowthandprogression. Citation:PanH,HanadaS,ZhaoJ,MaoL,MaMZ-Q(2012)Prot