| First Author | Ding S | Year | 2007 |
| Journal | Nutr Cancer | Volume | 58 |
| Issue | 2 | Pages | 153-61 |
| PubMed ID | 17640161 | Mgi Jnum | J:138109 |
| Mgi Id | MGI:3804176 | Doi | 10.1080/01635580701328248 |
| Citation | Ding S, et al. (2007) Adiposity-related protection of intestinal tumorigenesis: interaction with dietary calcium. Nutr Cancer 58(2):153-61 |
| abstractText | Although high-calcium diets have been reported to reduce the risk of colorectal cancer, our preliminary data with the adenomatous polyposis coli (Apc) Min mutation (Min/+;Apc(Min/+)) mouse shows a paradoxical increase in intestinal tumor loads (> 65%) with high calcium diets. Since we previously demonstrated that increasing dietary calcium reduces adiposity, and Apc(Min/+) mice on high calcium diets exhibited profound loss of adipose tissue, we hypothesized that loss of an adipose tissue-derived tumor suppressor factor(s) resulted in increased tumor susceptibility in animals on the high calcium diet. Accordingly, tumor prone Apc(Min/+) mice were crossed with obesity prone lethal yellow agouti (A(y)/a) mice to generate obese A(y)/Apc(Min/+) mice. Low (0.2%), normal (0.5%), and high (1.2%) calcium diets were fed to both A(y)/Apc(Min/+) mice and Apc(Min/+) mice from 35-40 days until 90 days of age (n=21/strain, n=7/diet group). The high calcium diet reduced weight gain in both strains (P < 0.01) and reduced fat pad mass by 46-57% in A(y)/Apc(Min/+)(P < 0.004) and by 65-82% in Apc(Min/+)(P < 0.03).Apc(Min/+) mice on the high calcium diet exhibited an increase in tumor number (76 vs. 29, P=0.009), but this effect was not seen in the A(y)/Apc(Min/+) mice. beta-Catenin and cyclin D1 gene expression were significantly induced with high calcium diet in intestinal tumor tissue of Apc(Min/+) mice but not in A(y)/Apc(Min/+) mice. We conclude that the differential effect of dietary calcium on intestinal tumorigenesis in lean vs. obese Apc(Min/+) may result from the loss of adipose-derived protective factor(s) due to the substantial loss of body fat in Apc(Min/+) mice fed a high calcium dairy diet, increasing beta-catenin and cyclin D1 in tumors. |
