Susceptibility of Snark-deficient mice to azoxymethane-induced colorectal tumorigenesis and the formation of aberrant crypt foci
Susceptibility of Snark-deficient mice to azoxymethane-induced colorectal tumorigenesis and the formation of aberrant crypt foci
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DOI：
10.1111/j.1349-7006.2008.00734.x
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发表时间：
2008-04-01
期刊：
影响因子：
5.7
通讯作者：
Esumi, Hiroyasu
中科院分区：
文献类型：
--
作者：
Tsuchihara, Katsuya;Ogura, Tsutomu;Esumi, Hiroyasu
SNF-1/5'-AMP 激活激酶 (AMPK) 相关激酶 (SNARK) 是 AMPK 相关激酶的成员。 Snark(+/-) 小鼠表现出成熟期肥胖和相关代谢紊乱。肥胖被认为是结直肠癌的危险因素。为了研究 Snark 缺陷是否与大肠肿瘤发生有关，用化学致癌剂氧化偶氮甲烷 (AOM) 治疗肥胖 Snark(+/-) 小鼠。完成 AOM 治疗（10 mg/kg/周，持续 8 周）后 28 周，Snark(+/-) 小鼠的腺瘤和异常隐窝病灶 (ACF) 的发生率显着高于野生型小鼠。此外，用 AOM 治疗 2 周的 Snark(+/-) 小鼠中 ACF 形成增强，表明 Snark 缺陷导致肿瘤发生的早期阶段。 Snark(+/-)和Snark(+/+)小鼠的ACF总数与体重相关，表明肥胖是该模型中结直肠肿瘤发生的危险因素。然而，Snark(+/-) 小鼠的相关系数较高。此外，在肥胖前期 Snark(+/-) 小鼠中，AOM 诱导的 ACF 形成也得到增强。总之，这些发现表明，AOM 诱导的 Snark(+/-) 小鼠肿瘤发生通过肥胖依赖性和非肥胖依赖性机制得到增强。
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.