N-myc oncogene overexpression down-regulates leukemia inhibitory factor in neuroblastoma

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dc.contributor.authorHatzi, E.en
dc.contributor.authorMurphy, C.en
dc.contributor.authorZoephel, A.en
dc.contributor.authorAhorn, H.en
dc.contributor.authorTontsch, U.en
dc.contributor.authorBamberger, A. M.en
dc.contributor.authorYamauchi-Takihara, K.en
dc.contributor.authorSchweigerer, L.en
dc.contributor.authorFotsis, T.en
dc.date.accessioned2015-11-24T19:01:57Z
dc.date.available2015-11-24T19:01:57Z
dc.identifier.issn0014-2956-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/19744
dc.rightsDefault Licence-
dc.subjectCell Division/drug effectsen
dc.subjectCulture Media, Conditioneden
dc.subjectDNA-Binding Proteins/genetics/metabolismen
dc.subjectDown-Regulationen
dc.subjectEndothelium/cytology/drug effectsen
dc.subjectGene Expression Regulation, Neoplasticen
dc.subjectGrowth Inhibitors/genetics/*metabolism/pharmacologyen
dc.subjectHumansen
dc.subject*Interleukin-6en
dc.subjectLeukemia Inhibitory Factoren
dc.subjectLymphokines/genetics/*metabolism/pharmacologyen
dc.subjectMutationen
dc.subjectNeuroblastoma/drug therapy/*genetics/pathologyen
dc.subjectPromoter Regions, Geneticen
dc.subjectProto-Oncogene Proteins c-myc/*genetics/metabolismen
dc.subjectSTAT3 Transcription Factoren
dc.subjectTrans-Activators/genetics/metabolismen
dc.subjectTransfectionen
dc.subjectTumor Cells, Cultureden
dc.titleN-myc oncogene overexpression down-regulates leukemia inhibitory factor in neuroblastomaen
heal.abstractAmplification of N-myc oncogene is a frequent event in advanced stages of human neuroblastoma and correlates with poor prognosis and enhanced neovascularization. Angiogenesis is an indispensable prerequisite for the progression and metastasis of solid malignancies, which is modulated by tumor suppressors and oncogenes. We have addressed the possibility that N-myc oncogene might regulate angiogenesis in neuroblastoma. Here, we report that experimental N-Myc overexpression results in down-regulation of leukemia inhibitory factor (LIF), a modulator of endothelial cell proliferation. Reporter assays using the LIF promoter and a series of N-Myc mutants clearly demonstrated that down-regulation of the LIF promoter was independent of Myc/Max interaction and required a contiguous N-terminal N-Myc domain. STAT3, a downstream signal transducer, was essential for LIF activity as infection with adenoviruses expressing a phosphorylation-deficient STAT3 mutant rendered endothelial cells insensitive to the antiproliferative action of LIF. LIF did not influence neuroblastoma cell proliferation suggesting that, at least in the context of neuroblastoma, LIF is involved in paracrine rather than autocrine interactions. Our data shed light on the mechanisms by which N-myc oncogene amplification enhances the malignant phenotype in neuroblastoma.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/12153570-
heal.identifier.secondaryhttp://onlinelibrary.wiley.com/store/10.1046/j.1432-1033.2002.03066.x/asset/j.1432-1033.2002.03066.x.pdf?v=1&t=h09a9iam&s=8d9d4eb089c353671b5a951da16c8d09f6eeafcd-
heal.journalNameEur J Biochemen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2002-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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