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dc.contributor.authorSaydam O.en_US
dc.contributor.authorGlauser, D.L.en_US
dc.contributor.authorHeid I.en_US
dc.contributor.authorTurkeri G.en_US
dc.contributor.authorHilbe, M.en_US
dc.contributor.authorJacobs, A.H.en_US
dc.contributor.authorAckermann, M.en_US
dc.contributor.authorFraefel, C.en_US
dc.date.accessioned2016-02-08T10:22:03Z
dc.date.available2016-02-08T10:22:03Z
dc.date.issued2005en_US
dc.identifier.issn15250016
dc.identifier.urihttp://hdl.handle.net/11693/23963
dc.description.abstractIn primary glioblastomas and other tumor types, the epidermal growth factor receptor (EGFR) is frequently observed with alterations, such as amplification, structural rearrangements, or overexpression of the gene, suggesting an important role in glial tumorigenesis and progression. In this study, we investigated whether posttranscriptional gene silencing by vector-mediated RNAi to inhibit EGFR expression can reduce the growth of cultured human gli36 glioma cells. To "knock down" EGFR expression, we have created HSV-1-based amplicons that contain the RNA polymerase III-dependent H1 promoter to express double-stranded hairpin RNA directed against EGFR at two different locations (pHSVsiEGFR I and pHSVsiEGFR II). We demonstrate that both pHSVsiEGFR I and pHSVsiEGFR II mediated knock-down of transiently transfected full-length EGFR or endogenous EGFR in a dose-dependent manner. The knock-down of EGFR resulted in the growth inhibition of human glioblastoma (gli36-luc) cells both in culture and in athymic mice in vivo. Cell cycle analysis and annexin V staining revealed that siRNA-mediated suppression of EGFR induced apoptosis. Overall HSV-1 amplicons can mediate efficient and specific posttranscriptional gene silencing. Copyright © The American Society of Gene Therapy.en_US
dc.language.isoEnglishen_US
dc.source.titleMolecular Therapyen_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.ymthe.2005.07.534en_US
dc.subjectEGFRen_US
dc.subjectHSV-1 ampliconsen_US
dc.subjectPosttranscriptional gene silencingen_US
dc.subjectTumor growthen_US
dc.subjectDNA directed RNA polymerase IIIen_US
dc.subjectdouble stranded RNAen_US
dc.subjectepidermal growth factor receptoren_US
dc.subjectlipocortin 5en_US
dc.subjectshort hairpin RNAen_US
dc.subjectsmall interfering RNAen_US
dc.subjectvirus vectoren_US
dc.subjectampliconen_US
dc.subjectanimal experimenten_US
dc.subjectanimal modelen_US
dc.subjectantineoplastic activityen_US
dc.subjectapoptosisen_US
dc.subjectarticleen_US
dc.subjectcancer inhibitionen_US
dc.subjectcell cycleen_US
dc.subjectcontrolled studyen_US
dc.subjectgene functionen_US
dc.subjectgene targetingen_US
dc.subjectgenetic transfectionen_US
dc.subjectgliomaen_US
dc.subjectHerpes simplex virus 1en_US
dc.subjecthumanen_US
dc.subjecthuman cellen_US
dc.subjectin vivo studyen_US
dc.subjectnonhumanen_US
dc.subjectnude mouseen_US
dc.subjectposttranscriptional gene silencingen_US
dc.subjectpromoter regionen_US
dc.subjectprotein domainen_US
dc.subjectprotein expressionen_US
dc.subjectRNA interferenceen_US
dc.subjecttumor cell cultureen_US
dc.subjectviral gene delivery systemen_US
dc.subjectGene Expression Regulation, Neoplasticen_US
dc.subjectGene Therapyen_US
dc.subjectGene Transfer Techniquesen_US
dc.subjectGenes, erbB-1en_US
dc.subjectGenetic Vectorsen_US
dc.subjectGlioblastomaen_US
dc.subjectHerpesvirus 1, Humanen_US
dc.subjectHumansen_US
dc.subjectReceptor, Epidermal Growth Factoren_US
dc.subjectRNA Interferenceen_US
dc.subjectRNA, Small Interferingen_US
dc.subjectTumor Cells, Cultureden_US
dc.subjectAnimaliaen_US
dc.subjectHuman herpesvirus 1en_US
dc.subjectMus musculusen_US
dc.titleHerpes simplex virus 1 amplicon vector-mediated siRNA targeting epidermal growth factor receptor inhibits growth of human glioma cells in vivoen_US
dc.typeArticleen_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.citation.spage803en_US
dc.citation.epage812en_US
dc.citation.volumeNumber12en_US
dc.citation.issueNumber5en_US
dc.identifier.doi10.1016/j.ymthe.2005.07.534en_US


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