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Expression analysis with oligonucleotide microarrays reveals that MYC regulates genes involved in growth, cell cycle,

H A Coller1, C Grandori, P Tamayo

  • 1Center for Genome Research, Whitehead Institute for Biomedical Research, Cambridge, MA 02139, USA. hcoller@fhcrc.org

Proceedings of the National Academy of Sciences of the United States of America
|March 29, 2000
PubMed

Insights

The MYC oncogene influences cell proliferation by altering gene expression. This study identified specific MYC target genes involved in cell growth, cell cycle, adhesion, and apoptosis, offering insights into cancer development.

Area of Science:

  • Molecular Biology
  • Oncology
  • Gene Regulation

Background:

  • The MYC oncogene plays a critical role in regulating cell proliferation, but its precise gene expression targets and pathways remain incompletely understood.
  • Understanding MYC's influence on gene expression is crucial for deciphering its role in both normal cellular processes and neoplastic transformation.

Purpose of the Study:

  • To comprehensively identify genes regulated by the c-MYC protein in primary human fibroblasts using a large-scale gene expression analysis.
  • To elucidate the functional pathways affected by MYC activation, including those related to cell growth, cell cycle, adhesion, and apoptosis.

Main Methods:

  • Oligonucleotide microarray analysis of 6,416 genes and expressed sequence tags to profile gene expression changes upon c-MYC activation.
  • Pattern-matching methods were employed to identify MYC target genes based on expression profiles in myeloid differentiation models.

Main Results:

  • Activation of c-MYC led to the consistent induction of 27 genes and repression of 9 genes.
  • Identified MYC targets include genes involved in cell growth (nucleolin, fibrillarin), cell cycle regulation (cyclin D2, p21(Cip1)), cell adhesion (fibronectin, collagen), and apoptosis (TRAP1).
  • Two immunophilins, peptidyl-prolyl cis-trans isomerase F and FKBP52, were upregulated by MYC.

Conclusions:

  • MYC significantly impacts diverse cellular processes, including growth, cell cycle progression, adhesion, and apoptosis, by modulating the expression of specific target genes.
  • The identified MYC target genes provide a molecular basis for MYC's oncogenic functions and suggest potential therapeutic targets.
  • Expression profiling and pattern-matching approaches are valuable for identifying MYC target genes and understanding their roles in cellular physiology and disease.

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