Nuclear Expression of KLF6 Tumor Suppressor Factor Is Highly Associated with Overexpression of ERBB2 Oncoprotein in Ductal Breast Carcinomas 英文参考文献.docVIP
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Nuclear Expression of KLF6 Tumor Suppressor Factor Is Highly Associated with Overexpression of ERBB2 Oncoprotein in Ductal Breast Carcinomas 英文参考文献
NuclearExpressionofKLF6TumorSuppressorFactorIs
HighlyAssociatedwithOverexpressionofERBB2
OncoproteininDuctalBreastCarcinomas
RicardoC.Gehrau1,DiegoS.D’Astolfo2,CatherineI.Dumur3,Jose′ L.Bocco1*,Nicola′sP.Koritschoner1
1Centro de Investigaciones en Bioqu?′mica Cl?′nica e Inmunolog?′a (CIBICI-CONICET), Departamento de Bioqu?′mica Cl?′nica, Facultad de Ciencias Qu?′micas, Universidad
NacionaldeCo′rdoba,Co′rdoba,Argentina,2CentrodeInvestigacionesenQu?′micaBiolo′gicadeCo′rdoba(CIQUIBIC-CONICET),FacultaddeCienciasQu?′micas,Universidad
NacionaldeCo′rdoba,Co′rdoba,Argentina,3DepartmentofPathology,VirginiaCommonwealthUniversity,Richmond,Virginia,UnitedStatesofAmerica
Abstract
Background:Kru¨ppel-likefactor6(KLF6)isanevolutionarilyconservedandubiquitouslyexpressedproteinthatbelongsto
themammalianSp1/KLF familyoftranscriptional regulators.ThoughKLF6 isatranscription factorandharborsanuclear
localizationsignalitisnotsystematicallylocatedinthenucleusbutitwasdetectedinthecytoplasmofseveraltissuesand
celllines.Hence,itisstillnotfullysettledwhetherthetumorsuppressorfunctionofKLF6isdirectlyassociatedwithitsability
toregulatetargetgenes.
Methodology/Principal Findings: In this study we analyzed KLF6 expression and sub-cellular distribution by
immunohistochemistry in several normal and tumor tissues in a microarray format representing fifteen human organs.
ResultsindicatethatwhilebothnuclearandcytoplasmicdistributionofKLF6isdetectedinnormalbreasttissues,breast
carcinomasexpressKLF6mainlydetectedinthecytoplasm.ExpressionofKLF6wasfurtheranalyzedinbreastcancertissues
overexpressingERBB2oncoprotein,whichisassociatedwithpoordiseaseprognosisandpatient’ssurvival.Theanalysisof
48 ductal carcinomas revealed a significant population expressing KLF6 predominantly in the nuclear compartment (X2
p=0.005; Fisher p=0.003). Moreover, this expression pattern correlates directly with early stage and small ductal breast
tumorsandlinkedtometastaticeventsinlymphnodes.
Conclusions/Significance
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