Regulation of MMP-9 (type IV collagenase) production and invasiveness in gliomas by the extracellular signal-regulated kinase and jun amino-terminal kinase signaling cascades

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dc.contributor.authorLakka, S. S.en
dc.contributor.authorJasti, S. L.en
dc.contributor.authorKyritsis, A. P.en
dc.contributor.authorYung, W. K.en
dc.contributor.authorAli-Osman, F.en
dc.contributor.authorNicolson, G. L.en
dc.contributor.authorRao, J. S.en
dc.date.accessioned2015-11-24T18:54:37Z
dc.date.available2015-11-24T18:54:37Z
dc.identifier.issn0262-0898-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/18708
dc.rightsDefault Licence-
dc.subjectBrain Neoplasms/enzymology/*pathologyen
dc.subjectEnzyme Inhibitors/pharmacologyen
dc.subjectFlavonoids/pharmacologyen
dc.subjectGlioma/enzymology/*pathologyen
dc.subjectHumansen
dc.subjectJNK Mitogen-Activated Protein Kinasesen
dc.subjectMatrix Metalloproteinase 9/*biosynthesis/geneticsen
dc.subjectMitogen-Activated Protein Kinase 3en
dc.subjectMitogen-Activated Protein Kinases/*metabolismen
dc.subjectPromoter Regions, Geneticen
dc.subject*Signal Transductionen
dc.subjectTranscriptional Activationen
dc.subjectTumor Cells, Cultureden
dc.titleRegulation of MMP-9 (type IV collagenase) production and invasiveness in gliomas by the extracellular signal-regulated kinase and jun amino-terminal kinase signaling cascadesen
heal.abstractOur previous studies have shown that MMP-9 levels are significantly elevated during the progression of human gliomas. In the current study, we examined the role of JNK- and ERK-dependent signaling modules in the regulation of MMP-9 production and the invasive behavior of the human glioblastoma cell line SNB19, in which JNK/ERK1 is constitutively activated. SNB19 cells that were transfected with dominant-negative JNK, MEKK, and ERK1 expression vectors showed reduced MMP-9 promoter activity. In addition, conditioned medium collected from SNB19 cells transfected with these expression vectors showed diminished MMP-9 activity in the presence of phorbol myristate acetate, as determined by gelatin zymography. The cotransfection of SNB19 cells with kinase-deficient c-raf also diminished MMP-9 promoter activity. Further, in the presence of a specific inhibitor of MEKK (PD098059), the Matrigel invasion assay showed the invasiveness of dominant-negative SNB19 cells transfected with dominant-negative JNK1 or ERK1 to be remarkably reduced. In conclusion, our studies showed for the first time that MMP-9 production and the invasive behavior of SNB 19 cells are regulated by JNK- and ERK-dependent signaling modules and that interfering with either of the pathways reduces invasiveness.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/11315098-
heal.journalNameClin Exp Metastasisen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2000-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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