Dual Role of Sp3 Transcription Factor as an Inducer of Apoptosis and a Marker of Tumour Aggressiveness 英文参考文献.docVIP

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Dual Role of Sp3 Transcription Factor as an Inducer of Apoptosis and a Marker of Tumour Aggressiveness 英文参考文献.doc

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Dual Role of Sp3 Transcription Factor as an Inducer of Apoptosis and a Marker of Tumour Aggressiveness 英文参考文献

DualRoleofSp3TranscriptionFactorasanInducerof ApoptosisandaMarkerofTumourAggressiveness KhadijaEssafi-Benkhadir1¤,Se′bastienGrosso2,AlexandrePuissant2,GuillaumeRobert2 ,Makram Essafi3,MarcelDeckert3,EmmanuelChamorey4,OlivierDassonville5,Ge′rardMilano6,PatrickAuberger2, GillesPage`s1* 1UniversityofNice-SophiaAntipolis,InstituteofDevelopmentalBiologyandCancerResearchUMRCNRS6543,CentreAntoineLacassagne,Nice,France,2Universityof Nice-SophiaAntipolis,INSERM,U895,CellDeathDifferentiationandCancerTeam,Equipelabellise′eparlaLigueNationalecontreleCancer,FacultyofMedicine,Nice, France, 3University of Nice-Sophia Antipolis, INSERM, U576, Regulation of immunity and inflammatory reactions, Nice, France, 4Statistic service, Centre Antoine Lacassagne,Nice,France,5Chirurgicalservice,CentreAntoineLacassagne,Nice,France,6Oncopharmacologyunit(EA3836),CentreAntoineLacassagne,Nice,France Abstract Background:TheambiguousroleoftranscriptionfactorSp3fortumourprogressionisstilldebatedsinceitwasdescribed as a transcriptional repressor or activator. Here we tried to decipher the molecular mechanisms implicated in Sp3 accumulationobservedinaggressivetumours. Methodology:WegeneratednormalandtumourcelllinesconditionallyexpressingSp3.Cellgrowthwasanalyzedinvitro andafterinoculationinnudemice.Apoptosiswasassessedbypan-caspaseactivityassays,bycountingfragmentednuclei andbydeterminationofcaspase9cleavage.GeneexpressionwasdeterminedbyquantitativePCR.Cleavagebydifferent caspaseswasperformedafterinvitrotranslationoftheSp3cDNAinthepresenceof[S35]labelledmethionine.Different tumourcelllinesandheadandnecktumoursamplesweretestedforthepresenceofSp3by westernblots.Correlation betweenSp3expressionandoverallsurvivalhasbeenstatisticallydetermined. PrincipalFindings:Conditionalover-expressionofSp3inducesapoptosisandmodifiesexpressionofgenesimplicatedin theregulationofcellcycleandproandantiapoptoticgenes.Sp3over-expression stronglyreducesthedevelopmentof tumours in nude mice confirming its pro-a