NSAID activated gene (NAG-1), a modulator of tumorigenesis

J Biochem Mol Biol. 2006 Nov 30;39(6):649-55. doi: 10.5483/bmbrep.2006.39.6.649.


The NSAID activated gene (NAG-1), a member of the TGF-beta superfamily, is involved in tumor progression and development. The over-expression of NAG-1 in cancer cells results in growth arrest and increase in apoptosis, suggesting that NAG-1 has anti-tumorigenic activity. This conclusion is further supported by results of experiments with transgenic mice that ubiquitously express human NAG-1. These transgenic mice are resistant to the development of intestinal tumors following treatment with azoxymethane or by introduction of a mutant APC gene. In contrast, other data suggest a pro-tumorigenic role for NAG-1, for example, high expression of NAG-1 is frequently observed in tumors. NAG-1 may be like other members of the TGF-beta superfamily, acting as a tumor suppressor in the early stages, but acting pro-tumorigenic at the later stages of tumor progression. The expression of NAG-1 can be increased by treatment with drugs and chemicals documented to prevent tumor formation and development. Most notable is the increase in NAG-1 expression by the inhibitors of cyclooxygenases that prevent human colorectal cancer development. The regulation of NAG-1 is complex, but these agents act through either p53 or EGR-1 related pathways. In addition, an increase in NAG-1 is observed in inhibition of the AKT/GSK-3beta pathway, suggesting NAG-1 alters cell survival. Thus, NAG-1 expression is regulated by tumor suppressor pathways and appears to modulate tumor progression.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Carcinogenicity Tests
  • Cell Transformation, Neoplastic / metabolism*
  • Cytokines / physiology*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Genes, Tumor Suppressor / physiology*
  • Growth Differentiation Factor 15
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Prostatic Neoplasms / metabolism
  • Transforming Growth Factor beta / chemistry
  • Transforming Growth Factor beta / metabolism


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • GDF15 protein, human
  • Gdf15 protein, mouse
  • Growth Differentiation Factor 15
  • Transforming Growth Factor beta