High susceptibility to azoxymethane-induced colorectal carcinogenesis in obese KK-Ay mice
Naoya Teraoka
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Michihiro Mutoh
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
Tel.: +81-3-3542-2511, Fax: +81-3-3542-9305
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo, JapanSearch for more papers by this authorShinji Takasu
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
Search for more papers by this authorToshiya Ueno
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
Search for more papers by this authorKatsuya Nakano
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
Search for more papers by this authorMami Takahashi
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
Search for more papers by this authorToshio Imai
Central Animal Laboratory, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
Search for more papers by this authorShuichi Masuda
Graduate School of Food and Nutritional Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan
Search for more papers by this authorTakashi Sugimura
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
Search for more papers by this authorKeiji Wakabayashi
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
Graduate School of Food and Nutritional Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan
Search for more papers by this authorNaoya Teraoka
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Michihiro Mutoh
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
Tel.: +81-3-3542-2511, Fax: +81-3-3542-9305
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo, JapanSearch for more papers by this authorShinji Takasu
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
Search for more papers by this authorToshiya Ueno
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
Search for more papers by this authorKatsuya Nakano
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
Search for more papers by this authorMami Takahashi
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
Search for more papers by this authorToshio Imai
Central Animal Laboratory, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
Search for more papers by this authorShuichi Masuda
Graduate School of Food and Nutritional Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan
Search for more papers by this authorTakashi Sugimura
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
Search for more papers by this authorKeiji Wakabayashi
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
Graduate School of Food and Nutritional Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan
Search for more papers by this authorAbstract
Obesity is associated with colon carcinogenesis. However, not much information is available regarding the mechanisms of obesity-associated colorectal cancer, and there are only few useful animal models for investigating the underlying mechanism between obesity and colorectal cancer. KK-Ay mice exhibit severe obesity. Amount of visceral fat assessed by micro-computed tomography was almost 15 times higher than that of same aged C57BL/6J mice. Treatment with azoxymethane (AOM; 200 μg/mouse injected once a week for 3 times) resulted in markedly increased colon aberrant crypt foci (ACF) development (≈70 ACF/mouse) in KK-Ay mice compared with lean C57BL/6J mice (≈9 ACF/mouse). Moreover, administration of AOM at a dose of 200 μg/mouse once a week for 6 times developed colorectal adenocarcinomas within only 7 weeks after the last AOM injection. The incidence of adenocarcinoma was 88% in KK-Ay mice and was markedly higher than the 4% observed in C57BL/6J mice. The number of tumors/mouse was 7.80 in KK-Ay mice and also markedly higher than the 0.12 in the C57BL/6J case. Interestingly, adenocarcinomas were observed in most of the AOM-treated KK-Ay mice along with remarkable tumor angiogenesis, and some showed submucosal invasion. These results indicate that the KK-Ay mouse, featuring intact leptin and leptin receptor Ob-Rbl, could be a useful animal model to investigate obesity-associated cancer.
Supporting Information
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| Filename | Description |
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| IJC_25711sm_supptable1.doc40.5 KB | Supporting Table 1. |
| IJC_25711sm_supptable2.doc28.5 KB | Supporting Table 2. |
| IJC_25711sm_supptable3.doc27.5 KB | Supporting Table 3. |
| IJC_25711sm_supptable4.doc28 KB | Supporting Table 4. |
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