N-myc oncogene overexpression down-regulates IL-6; evidence that IL-6 inhibits angiogenesis and suppresses neuroblastoma tumor growth

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dc.contributor.authorHatzi, E.en
dc.contributor.authorMurphy, C.en
dc.contributor.authorZoephel, A.en
dc.contributor.authorRasmussen, H.en
dc.contributor.authorMorbidelli, L.en
dc.contributor.authorAhorn, H.en
dc.contributor.authorKunisada, K.en
dc.contributor.authorTontsch, U.en
dc.contributor.authorKlenk, M.en
dc.contributor.authorYamauchi-Takihara, K.en
dc.contributor.authorZiche, M.en
dc.contributor.authorRofstad, E. K.en
dc.contributor.authorSchweigerer, L.en
dc.contributor.authorFotsis, T.en
dc.date.accessioned2015-11-24T19:01:58Z
dc.date.available2015-11-24T19:01:58Z
dc.identifier.issn0950-9232-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/19745
dc.rightsDefault Licence-
dc.subjectAngiogenesis Inhibitors/metabolism/pharmacology/*physiologyen
dc.subjectAnimalsen
dc.subjectAntineoplastic Agents/metabolism/pharmacologyen
dc.subjectCattleen
dc.subjectCell Division/drug effectsen
dc.subjectCells, Cultureden
dc.subjectCentral Nervous System Neoplasms/blood supply/metabolism/pathology/therapyen
dc.subjectCornea/blood supply/drug effectsen
dc.subjectDNA-Binding Proteins/metabolismen
dc.subjectDown-Regulationen
dc.subjectEndothelium, Vascular/cytology/drug effectsen
dc.subjectFemaleen
dc.subjectGene Expression Regulation, Neoplasticen
dc.subjectInterleukin-6/*metabolism/pharmacology/*physiologyen
dc.subjectMiceen
dc.subjectMice, Inbred BALB Cen
dc.subjectMice, Nudeen
dc.subject*Neovascularization, Pathologic/therapyen
dc.subjectNeuroblastoma/*blood supply/metabolism/pathology/therapyen
dc.subjectOncogene Protein p55(v-myc)/*genetics/metabolismen
dc.subjectRNA, Neoplasm/biosynthesisen
dc.subjectRabbitsen
dc.subjectSTAT3 Transcription Factoren
dc.subjectTrans-Activators/metabolismen
dc.subjectTransfectionen
dc.subjectTumor Cells, Cultureden
dc.titleN-myc oncogene overexpression down-regulates IL-6; evidence that IL-6 inhibits angiogenesis and suppresses neuroblastoma tumor growthen
heal.abstractAngiogenesis is an indispensable prerequisite for the progression and metastasis of solid malignancies. Tumor angiogenesis appears to be governed by alterations of tumor suppressor or oncogenes operant in a broad range of tumors. We have addressed this issue in neuroblastoma, a malignancy characterized by the near-exclusive amplification and overexpression of the N-Myc oncogene. Here, we report that N-Myc overexpression results in down-regulation of interleukin-6 (IL-6) and that IL-6 is an inhibitor of endothelial cell proliferation and VEGF-induced rabbit corneal angiogenesis. STAT3 is instrumental for IL-6 activity as infection with adenoviruses expressing a phosphorylation deficient STAT3 mutant renders endothelial cells insensitive to the antiproliferative action of IL-6. Finally, though IL-6 does not influence neuroblastoma cell growth, IL-6-expressing xenograft tumors in mice exhibit reduced neovascularization and suppressed growth. Our data shed new light on the mechanisms by which N-myc oncogene amplification enhances the malignant phenotype in neuroblastomas.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.primary10.1038/sj.onc.1205440-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/12032857-
heal.identifier.secondaryhttp://www.nature.com/onc/journal/v21/n22/pdf/1205440a.pdf-
heal.journalNameOncogeneen
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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