Potential Downstream Target Genes of Aberrant ETS Transcription Factors Are Differentially Affected in Ewing’s Sarcoma and Prostate Carcinoma 英文参考文献.docVIP
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Potential Downstream Target Genes of Aberrant ETS Transcription Factors Are Differentially Affected in Ewing’s Sarcoma and Prostate Carcinoma 英文参考文献
PotentialDownstreamTargetGenesofAberrantETS
TranscriptionFactorsAreDifferentiallyAffectedin
Ewing’sSarcomaandProstateCarcinoma
MariaJ.Camo?es1,2.,PaulaPaulo1,2.,FranclimR.Ribeiro1,2,Joa?oD.Barros-Silva1,2,MafaldaAlmeida1,3
,
VeraL.Costa1,3,NunoCerveira1,2,RolfI.Skotheim4,5,RagnhildA.Lothe4,5,RuiHenrique3,6,7
CarmenJero′nimo1,3,7,ManuelR.Teixeira1,2,5,7
,
*
1DepartmentofGenetics,PortugueseOncologyInstitute-Porto,Porto,Portugal,2CancerGeneticsGroup,ResearchCentreofthePortugueseOncologyInstitute-Porto,
Porto,Portugal, 3CancerEpigenetics Group,ResearchCentreofThePortuguese OncologyInstitute, Porto, Portugal, 4Department ofCancerPrevention, Institute for
Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway, 5Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo,
Norway, 6Department of Pathology, Portuguese Oncology Institute-Porto, Porto, Portugal, 7Department of Pathology and Molecular Immunology, Institute of
BiomedicalSciencesAbelSalazar(ICBAS),UniversityofPorto,Porto,Portugal
Abstract
FLI1andERG,themajorETStranscriptionfactorsinvolvedinrearrangementsintheEwing’ssarcomafamilyoftumors(ESFT)
andinprostatecarcinomas(PCa),respectively,belongtothesamesubfamily,having98%sequenceidentityintheDNA
bindingdomain.Wethereforedecidedtoinvestigatewhethertheaberranttranscriptionfactorsinbothmalignancieshave
somecommondownstreamtargets.WecrossedapubliclyavailablelistofallputativeEWSR1-FLI1targetgenesinESFTwith
ourmicroarrayexpressiondataon24PCaand6non-malignantprostatetissues(NPT)andchoosefourgenesamongthe
top-mostdifferentiallyexpressedbetweenPCawith(PCaERG+)andwithout(PCaETS-)ETSfusiongenes(HIST1H4L,KCNN2,
ECRG4andLDOC1),aswellasfourwell-validateddirecttargetsoftheEWSR1-FLI1chimericproteininESFT(NR0B1,CAV1,
IGFBP3andTGFBR2).Usingquantitativeexpressionanalysisin16ESFTandsevenalveolarrhabdomyosarcomas(ARMS),we
were able to validate the four genes previously described as direct targets of the EWSR1-FLI1 oncoprotein, showing
ove
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