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E2F proteins regulate MYCN expression in neuroblastomas.

Verena Strieder·Werner Lutz
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Abstract

Amplification of the MYCN gene, resulting in overexpression of MYCN, distinguishes a subset of neuroblastomas with poor prognosis. The transcription factors driving MYCN expression in neuroblastomas are unknown. In transient-transfection assays, E2F-1, E2F-2, and E2F-3 activate a MYCN reporter construct dependent on the presence of several putative E2F-binding sites. Using chromatin immunoprecipitation, we show that E2F-1, E2F-2, and E2F-3 bind to the proximal MYCN promoter in vivo, specifically in neuroblastoma cell lines expressing MYCN. Inhibition of E2F activity in MYCN-amplified cells by the overexpression of p16(INK4A) reduced MYCN expression. In addition, we provide evidence that E2F proteins are involved in the negative regulation of MYCN by TGF-beta and retinoic acid. These data suggest that E2F transcription factors are critical for both the full activation and the repression of MYCN in neuroblastomas.

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Base SequenceBinding SitesCell Cycle ProteinsCyclin-Dependent Kinase Inhibitor p16DNA-Binding ProteinsE2F Transcription FactorsE2F1 Transcription FactorE2F2 Transcription FactorE2F3 Transcription FactorGene Expression Regulation, NeoplasticHumansN-Myc Proto-Oncogene ProteinNeuroblastomaNuclear ProteinsOncogene ProteinsPromoter Regions, GeneticTranscription FactorsTranscription, GeneticTransfectionTransforming Growth Factor betaTretinoinTumor Cells, CulturedJournal ArticleResearch Support, Non-U.S. Gov't

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Verena Strieder, Werner Lutz. 2002-11-15. E2F proteins regulate MYCN expression in neuroblastomas.. https://doi.org/10.1074/jbc.m207596200

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