High susceptibility to azoxymethane-induced colorectal carcinogenesis in obese KK-Ay mice.
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-A(y) 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-A(y) 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-A(y) mice and was markedly higher than the 4% observed in C57BL/6J mice. The number of tumors/mouse was 7.80 in KK-A(y) 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-A(y) mice along with remarkable tumor angiogenesis, and some showed submucosal invasion. These results indicate that the KK-A(y) mouse, featuring intact leptin and leptin receptor Ob-Rbl, could be a useful animal model to investigate obesity-associated cancer.
Teraoka
Naoya
N
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
Mutoh
Michihiro
M
Takasu
Shinji
S
Ueno
Toshiya
T
Nakano
Katsuya
K
Takahashi
Mami
M
Imai
Toshio
T
Masuda
Shuichi
S
Sugimura
Takashi
T
Wakabayashi
Keiji
K
D058739:Aberrant Crypt Foci / Q000139:chemically induced; D000230:Adenocarcinoma / Q000139:chemically induced* / Q000453:epidemiology / Q000473:pathology; D000818:Animals; D001397:Azoxymethane; D002273:Carcinogens; D015179:Colorectal Neoplasms / Q000139:chemically induced* / Q000453:epidemiology / Q000473:pathology; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D015994:Incidence; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D054411:Receptors, Leptin / Q000378:metabolism
D002273:Carcinogens; D054411:Receptors, Leptin; D001397:Azoxymethane