Direct regulation of the minichromosome maintenance complex by MYCN in neuroblastoma

Research output: Contribution to journalArticle

Abstract

The c-Myc and MYCN oncogenes strongly induce cell proliferation. Although a limited series of cell cycle genes were found to be induced by the myc transcription factors, it is still unclear how they mediate the proliferative phenotype. We therefore analysed a neuroblastoma cell line with inducible MYCN expression. We found that all members of the minichromosome maintenance complex (MCM2 - 7) and MCM8 and MCM10 were up-regulated by MYCN. Expression profiling of 110 neuroblastoma tumours revealed that these genes strongly correlated with MYCN expression in vivo. Extensive chromatin immunoprecipitation experiments were performed to investigate whether the MCM genes were primary MYCN targets. MYCN was bound to the proximal promoters of the MCM2 to -8 genes. These data suggest that MYCN stimulates the expression of not only MCM7, which is a well defined MYCN target gene, but also of the complete minichromosome maintenance complex. (c) 2007 Elsevier Ltd. All rights reserved.

Details

Authors
  • Arjen Koppen
  • Rachida Ait-Aissa
  • Jan Koster
  • Peter G. van Sluis
  • Ingrid Øra
  • Huib N. Caron
  • Richard Volckmann
  • Rogier Versteeg
  • Linda J. Valentijn
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Pediatrics

Keywords

  • MCM, DNA replication, MYCN, neuroblastoma
Original languageEnglish
Pages (from-to)2413-2422
JournalEuropean Journal of Cancer
Volume43
Issue number16
Publication statusPublished - 2007
Publication categoryResearch
Peer-reviewedYes