Direct regulation of the minichromosome maintenance complex by MYCN in neuroblastoma.
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.
Koppen
Arjen
A
Department of Human Genetics, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands.
Ait-Aissa
Rachida
R
Koster
Jan
J
van Sluis
Peter G
PG
Ora
Ingrid
I
Caron
Huib N
HN
Volckmann
Richard
R
Versteeg
Rogier
R
Valentijn
Linda J
LJ
D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics*; D002454:Cell Differentiation; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D016259:Genes, myc; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D064111:Minichromosome Maintenance Complex Component 2; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins