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N-myc enhances the expression of a large set of genes functioning in ribosome biogenesis and protein synthesis

K Boon1, H N Caron, R van Asperen

  • 1Department of Human Genetics, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands.

The EMBO Journal
|March 17, 2001
PubMed

Insights

Myc oncogenes regulate protein synthesis. N-myc transcription factor targets genes involved in ribosome assembly and activity, impacting neuroblastoma tumor growth.

Area of Science:

  • Molecular Biology
  • Oncology
  • Gene Regulation

Background:

  • Myc oncogenes are frequently activated in human tumors.
  • Comprehensive understanding of myc target genes and downstream pathways is lacking.

Purpose of the Study:

  • To identify N-myc target genes in neuroblastomas using SAGE.
  • To investigate the role of N-myc in regulating cellular pathways.

Main Methods:

  • Serial Analysis of Gene Expression (SAGE) was used to analyze mRNA transcripts in N-myc-transfected and control neuroblastoma cells.
  • Northern blot analysis was performed to confirm gene up-regulation.
  • N-myc targets were also analyzed in c-myc-transfected melanoma cells.

Main Results:

  • 114 genes were up-regulated by N-myc, predominantly involved in ribosome assembly and activity.
  • N-myc induction of these genes was rapid (within 4 hours).
  • Up-regulation of ribosomal proteins, rRNA maturation genes, and cellular rRNA content was observed.
  • Many identified N-myc targets were also up-regulated in N-myc-amplified neuroblastomas.
  • Approximately 40% of N-myc targets were induced by c-myc.

Conclusions:

  • Myc genes, including N-myc, are major regulators of the protein synthesis machinery.
  • N-myc plays a significant role in ribosome biogenesis and activity in neuroblastoma.
  • The findings provide insight into the downstream effects of myc oncogene activation in cancer.

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