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

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. (Cancer Sci 2008; 99: 677–682)