Circulating insulin-like growth factor I (IGF-I) is associated with increased risk of colorectal cancer. It is not clear, however, whether IGF-1 plays a direct causative role in colon carcinogenesis or whether it mediates the known promoting effects of insulin. The objective of this study was to determine the role of IGF-1 in colon carcinogenesis using liver-specific IGF-I deficient (LID) mice that exhibit 70% reductions in circulating IGF-I. Female and male LID mice were treated with the colon-specific carcinogen azoxymethane to induce aberrant crypt foci (ACF) or colon tumors. Female LID mice developed significantly fewer ACF and had normal insulin levels compared to controls. Male LID mice, however, were hyperinsulinemic and exhibited no significant differences in ACF development compared to controls. In the tumor study, both male and female LID mice were hyperinsulinemic and had no significant differences in tumor incidence or multiplicity compared to their respective controls. There was a significant 25% reduction in tumor size, however, in both male and female LID mice compared to controls. These data suggest that IGF-I deficiency attenuates the promoting effect of insulin on colon carcinogenesis and that IGF-I is an independent promoter of the growth of established tumors. Our findings implicate both IGF-I and insulin as important promoters of colon cancer development.
Copyright 2007 Wiley-Liss, Inc.