N-myc enhances the expression of a large set of genes functioning in ribosome biogenesis and protein synthesis.
The myc oncogenes are frequently activated in human tumors, but there is no comprehensive insight into the target genes and downstream cellular pathways of these transcription factors. We applied serial analysis of gene expression (SAGE) to identify targets of N-myc in neuroblastomas. Analysis of 42,000 mRNA transcript tags in SAGE libraries of N-myc- transfected and control neuroblastoma cells revealed 114 up-regulated genes. The majority of these genes have a role in ribosome assembly and activity. Northern blot analysis confirmed up-regulation of all tested transcripts. Induction was complete within 4 h after N-myc expression. The large majority of the ribosomal proteins were induced, as well as genes controlling rRNA maturation. Cellular rRNA content was 45% induced. SAGE libraries and northern blot analysis confirmed up-regulation of many of these genes in N-myc-amplified neuroblastomas. As N-myc can functionally replace c-myc, we analyzed whether N-myc targets were induced by c-myc as well. Approximately 40% of these N-myc targets were up-regulated in a c-myc-transfected melanoma cell line. These data suggest that myc genes function as major regulators of the protein synthesis machinery.
Department of Human Genetics, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands.
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K
Boon
H N
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Caron
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van Asperen
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L
Valentijn
M C
MC
Hermus
P
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van Sluis
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I
Roobeek
I
I
Weis
P A
PA
Voûte
M
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Schwab
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Versteeg
D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D015723:Gene Library; D016259:Genes, myc / Q000235:genetics*; D006019:Glycolysis / Q000235:genetics; D006801:Humans; D008546:Melanoma, Experimental / Q000235:genetics; D009447:Neuroblastoma / Q000235:genetics*; D014176:Protein Biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012335:RNA, Ribosomal / Q000096:biosynthesis; D012269:Ribosomal Proteins / Q000096:biosynthesis / Q000235:genetics; D012270:Ribosomes / Q000235:genetics*; D013997:Time Factors; D015854:Up-Regulation
D012333:RNA, Messenger; D012335:RNA, Ribosomal; D012269:Ribosomal Proteins