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dc.contributor.authorHuang, Ruimin
dc.contributor.authorCheung, Nai-Kong V
dc.contributor.authorVider, Jelena
dc.contributor.authorCheung, Irene Y
dc.contributor.authorGerald, William L
dc.contributor.authorTickoo, Satish K
dc.contributor.authorHolland, Eric C
dc.contributor.authorBlasberg, Ronald G
dc.date.accessioned2017-05-03T16:06:18Z
dc.date.available2017-05-03T16:06:18Z
dc.date.issued2011
dc.identifier.issn0892-6638
dc.identifier.doi10.1096/fj.11-185033
dc.identifier.urihttp://hdl.handle.net/10072/44889
dc.description.abstractThe BMI1 gene is overexpressed in 蠹0% of human neuroblastomas. However, little is known about the regulation of BMI1 expression. Using microarray and immunohistochemical analysis, we show that BMI1 expression correlated with MYCN levels in MYCN-amplified human neuroblastomas, and with MYC levels in the MYCN-nonamplified group. We further demonstrated that BMI1 is a direct target gene of MYCN/MYC in 3 neuroblastoma cell lines: BE (2)-C, LAN1, and SH-SY5Y. Overexpression of MYCN or MYC transactivated the BMI1 promoter and up-regulated BMI1 gene expression. shRNA-mediated knockdown of MYCN or MYC decreased BMI1 gene expression. Chromatin immunoprecipitation and point-mutation assays revealed that both MYCN and MYC bind to the E-box within the BMI1 promoter. Overexpression of BMI1, MYCN, and MYC independently increased both cell proliferation and tumor growth. Conversely, specific inhibition of BMI1, MYCN, and MYC decreased tumor cell proliferation and tumor growth. Interestingly, BMI1 suppression in MYCN/MYC-overexpressing cells resulted in significantly greater inhibition compared to that in mock-transduced and parental cells. Our results indicate that MYCN and MYC regulate BMI1 gene expression at the transcriptional level and that dysregulation of the BMI1 gene mediated by MYCN or MYC overexpression, confers increased cell proliferation during neuroblastoma genesis and tumor progression.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherFederation of American Societies for Experimental Biology
dc.publisher.placeAmerica
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom4138
dc.relation.ispartofpageto4149
dc.relation.ispartofissue12
dc.relation.ispartofjournalThe FASEB Journal
dc.relation.ispartofvolume25
dc.rights.retentionY
dc.subject.fieldofresearchCancer Cell Biology
dc.subject.fieldofresearchBiochemistry and Cell Biology
dc.subject.fieldofresearchPhysiology
dc.subject.fieldofresearchMedical Physiology
dc.subject.fieldofresearchcode111201
dc.subject.fieldofresearchcode0601
dc.subject.fieldofresearchcode0606
dc.subject.fieldofresearchcode1116
dc.titleMYCN and MYC regulate tumor proliferation and tumorigenesis directly through BMI1 in human neuroblastomas
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.rights.copyrightSelf-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the author for more information.
gro.date.issued2015-06-12T05:04:03Z
gro.hasfulltextNo Full Text
gro.griffith.authorVider, Jelena


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