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Obesity is a known risk factor for several types of cancers including colorectal and breast carcinomas. However, the factors mediating the obesity-cancer link have not been fully elucidated. To evaluate the role of the type 1 insulin-like growth factor (IGF-I) in obesity-related enhancement of tumor growth, we utilized the liver IGF-I deficiency (LID) mouse model recently developed using the Cre/lox P recombination system. We have previously shown that LID mice have a liver-specific deletion of the igf1 gene, resulting in a 75% reduction in circulating IGF-I levels. We have also reported that LID mice, when crossed with mammary tumor-susceptible SV40-LTA transgenic mice or when treated with the carcinogen DMBA or implanted with mouse colon 38 adenocarcinoma, display a reduced incidence of tumors. In the present study, male and female LID mice and their wild-type littermate controls were either fed high-calorie diet or control (moderate calorie) diet. Mice on the high-calorie diet, regardless of genotype, became obese (relative to mice on control diet) by 10 weeks of age as evidenced by a three-fold increase in white adipose tissue mass, impaired glucose metabolism and increased insulin resistance. All mice were injected subcutaneously with the syngeneic colon 38 adenocarcinoma or Lewis lung carcinoma cells and tumor growth was monitored. We found that tumor growth in obese wild-type mice was significantly increased as compared to mice fed the control diet. However, in the face of IGF-1 deficiency in the LID mice, obesity did not increase tumor growth. In fact, the tumor growth rate in obese LID mice was lower than that observed in non-obese wild-type mice. These results identify IGF-I as one of the factors contributing to increased tumor growth in the obese animals.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]