Susceptibility of Snark-deficient mice to azoxymethane-induced colorectal tumorigenesis and the formation of aberrant crypt foci

Cancer Sci. 2008 Apr;99(4):677-82. doi: 10.1111/j.1349-7006.2008.00734.x. Epub 2007 Feb 27.

Abstract

SNF-1/5'-AMP-activated kinase (AMPK)-related kinase (SNARK) is a member of the AMPK-related kinases. Snark(+/-) mice exhibited mature-onset obesity and related metabolic disorders. Obesity is regarded as a risk factor for colorectal cancer. To investigate whether Snark deficiency is involved in tumorigenesis in the large intestine, obese Snark(+/-) mice were treated with a chemical carcinogen, azoxymethane (AOM). The incidences of both adenomas and aberrant crypt foci (ACF) were significantly higher in Snark(+/-) mice than in their wild-type counterparts 28 weeks after the completion of AOM treatment (10 mg/kg/week for 8 weeks). Furthermore, ACF formation was enhanced in Snark(+/-) mice treated with AOM for 2 weeks, suggesting that Snark deficiency contributed to the early phase of tumorigenesis. The total number of ACF was correlated with bodyweight in Snark(+/-) and Snark(+/+) mice, suggesting that obesity was a risk factor for colorectal tumorigenesis in this model. However, the correlation coefficient was higher in Snark(+/-) mice. Moreover, AOM-induced ACF formation was also enhanced in preobese Snark(+/-) mice. Together, these findings suggest that AOM-induced tumorigenesis in Snark(+/-) mice was enhanced via obesity-dependent and -independent mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azoxymethane / toxicity
  • Body Weight
  • Carcinogens / toxicity
  • Colorectal Neoplasms / chemically induced
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Female
  • Gastrointestinal Tract / enzymology
  • Gastrointestinal Tract / pathology
  • Genetic Predisposition to Disease*
  • Mice
  • Mice, Mutant Strains
  • Obesity / complications
  • Obesity / genetics*
  • Precancerous Conditions / chemically induced
  • Precancerous Conditions / genetics*
  • Precancerous Conditions / pathology
  • Protein Serine-Threonine Kinases / genetics*
  • Risk Factors

Substances

  • Carcinogens
  • Snrk protein, mouse
  • Protein Serine-Threonine Kinases
  • Azoxymethane