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Gas6 and the Receptor Tyrosine Kinase Axl in Clear Cell Renal Cell Carcinoma 英文参考文献
Gas6andtheReceptorTyrosineKinaseAxlinClearCell
RenalCellCarcinoma
AnnaGustafsson1.,Anna-KarinBostro¨m2.,Bo¨rjeLjungberg3,Ha?kanAxelson2,Bjo¨rnDahlba¨ck1*
1DepartmentofLaboratoryMedicine,SectionforClinicalChemistry,UniversityHospitalMalmo¨,LundUniversity,Malmo¨,Sweden,2DepartmentofLaboratoryMedicine,
Center for Molecular Pathology, University Hospital Malmo¨, Lund University, Malmo¨, Sweden, 3Department of Surgical and Perioperative Sciences, Urology and
Andrology,Umea? University,Umea?, Sweden
Abstract
Background:Themolecularbiologyofrenalcellcarcinoma(RCC)iscomplexandnotfullyunderstood.Wehaverecently
foundthattheexpressionofthereceptortyrosinekinaseAxlintheRCCtumorsindependentlycorrelateswithsurvivalof
thepatients.
PrincipalFindings:Here,wehaveinvestigatedtheroleofAxlanditsligandGas6,thevitamin-Kdependentproteinproduct
ofthegrowtharrest-specificgene6,inclearcellRCC(ccRCC)derivedcells.TheAxlproteinwashighlyexpressedinccRCC
cells deficient in functional von Hippel-Lindau (VHL) protein, a tumor suppressor gene often inactivated in ccRCC. VHL
reconstitutedcellsexpresseddecreasedlevelsofAxlprotein,butnotAxlmRNA,suggestingVHLtoregulateAxlexpression.
Gas6-mediatedactivationofAxlinccRCCcellsresultedinAxlphosphorylation,receptordown-regulation,decreasedcell-
viabilityandmigratorycapacity.NoeffectsoftheGas6/Axlsystemcouldbedetectedoninvasion.Moreover,inccRCCtumor
tissues,AxlwasphosphorylatedandGas6c-carboxylated,suggestingthesemoleculestobeactiveinvivo.
Significance:TheseresultsprovidenovelinformationregardingthecomplexfunctionoftheGas6/AxlsysteminccRCC.
Citation: Gustafsson A, Bostro¨m A-K, Ljungberg B, Axelson H, Dahlba¨ck B (2009) Gas6 and the Receptor Tyrosine Kinase Axl in Clear Cell Renal Cell
Carcinoma.PLoSONE4(10):e7575.doi:10.1371/journal.pone.0007575
Editor:SyedA.Aziz,HealthCanada,Canada
ReceivedSeptember3,2009;AcceptedOctober5,2009;PublishedOctober30,2009
Copyright: ?2009 Gustafsson etal.This isanopen-accessarticledistributedunder thetermsofthe Creative Comm
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