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

被引：25

作者：

Tsuchihara, Katsuya ^{[2
]}

Ogura, Tsutomu ^{[3
]}

Fujioka, Rumi ^{[2
]}

Fujii, Satoshi ^{[1
]}

Kuga, Wataru ^{[2
,4
]}

Saito, Marie ^{[2
,4
]}

Ochiya, Takahiro ^{[5
]}

Ochiai, Atsushi ^{[1
,4
]}

Esumi, Hiroyasu ^{[2
,4
]}

机构：

[1] Natl Canc Ctr Hosp, Res Ctr Innovat Oncol, Div Pathol, Kashiwa, Chiba 2778577, Japan

[2] Natl Canc Ctr Hosp, Res Ctr Innovat Oncol, Canc Physiol Project, Kashiwa, Chiba 2778577, Japan

[3] Hokuriku Univ, Fac Pharmaceut Sci, Dept Bioinformat Sci, Kanazawa, Ishikawa 9201180, Japan

[4] Natl Canc Ctr Hosp, Grad Sch Frontier Sci, Dept Integrated Sci, Kashiwa, Chiba 2778561, Japan

[5] Natl Canc Ctr, Res Inst, Sect Studies Metastasis, Tokyo 1040045, Japan

来源：

CANCER SCIENCE | 2008年 / 99卷 / 04期

关键词：

D O I：

10.1111/j.1349-7006.2008.00734.x

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：677 / 682

页数：6

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