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.
Tsuchihara
Katsuya
K
Cancer Physiology Project, Research Center for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
Ogura
Tsutomu
T
Fujioka
Rumi
R
Fujii
Satoshi
S
Kuga
Wataru
W
Saito
Marie
M
Ochiya
Takahiro
T
Ochiai
Atsushi
A
Esumi
Hiroyasu
H
D000818:Animals; D001397:Azoxymethane / Q000633:toxicity; D001835:Body Weight; D002273:Carcinogens / Q000633:toxicity; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D005260:Female; D041981:Gastrointestinal Tract / Q000201:enzymology / Q000473:pathology; D020022:Genetic Predisposition to Disease; D051379:Mice; D008817:Mice, Mutant Strains; D009765:Obesity / Q000150:complications / Q000235:genetics*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors
D002273:Carcinogens; C490993:Snrk protein, mouse; D017346:Protein Serine-Threonine Kinases; D001397:Azoxymethane