ADP Ribosylation Factor Like 2 (Arl2) Regulates Breast Tumor Aggressivity in Immunodeficient Mice 英文参考文献.docVIP
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ADP Ribosylation Factor Like 2 (Arl2) Regulates Breast Tumor Aggressivity in Immunodeficient Mice 英文参考文献
ADPRibosylationFactorLike2(Arl2)RegulatesBreast
TumorAggressivityinImmunodeficientMice
AnneBeghin1,2.,Ste′phaneBelin3.,RoubaHageSleiman1,2,Ste′phanieBrunetManquat1,2 ,Sophie
Goddard4,EricTabone4,LarsP.Jordheim1,2,IsabelleTreilleux4,Marie-FrancePoupon5 ,Jean-Jacques
Diaz3,CharlesDumontet1,2*
1Inserm,U590,Lyon,France,2Universite′ Lyon1,ISPB,Lyon,France,3CNRS,CentredeGe′ne′tiqueMole′culaireetCellulaire,UMR5534,Villeurbanne,France,4Centre
Le′onBe′rard,ServiceAnatomie-CytologiePathologiques,Lyon,France,5InstitutCurie,Paris,France
Abstract
We have previously reported that ADP ribosylation factor like 2 (Arl2), a small GTPase, content influences microtubule
dynamicsandcellcycledistributioninbreasttumorcells,aswellasthedegreeanddistributionofphosphorylatedP53.Here
weshow,intwodifferenthumanbreastadenocarcinomamodels,thatArl2contenthasamajorimpactonbreasttumorcell
aggressivity both invitro and in vivo. Cellswith reduced contentof Arl2 displayed reducedcontact inhibition, increased
clonogenicorclusterformationaswellasaproliferativeadvantageovercontrolcellsinaninvitrocompetitionassay.These
cells also caused larger tumors in SCID mice, a phenotype which was mimicked by the in vivo administration of siRNA
directed against Arl2. Cells with increased Arl2 content displayed reduced aggressivity, both in vitro and in vivo , with
enhancednecrosisandwerealsofoundtocontainincreasedPP2Aphosphataseactivity.Art-PCRanalysisoffreshhuman
tumorbreastsamplessuggestedthatlowArl2expressionwasassociatedwithlargertumorsizeandgreaterriskoflymph
nodeinvolvementatdiagnosis.ThesedataunderlinetheroleofArl2,asmallGTPase,asanimportantregulatorofbreast
tumorcellaggressivity,bothinvitroandinvivo.
Citation:BeghinA,BelinS,HageSleimanR,BrunetManquatS,GoddardS,etal.(2009)ADPRibosylationFactorLike2(Arl2)RegulatesBreastTumorAggressivity
inImmunodeficientMice.PLoSONE4(10):e7478.doi:10.1371/journal.pone.0007478
Editor:SyedA.Aziz,HealthCanada,Canada
ReceivedJune17,2009;AcceptedSeptember2,2009;PublishedOctober15
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