Inulin results in increased levels of beta-catenin and cyclin D1 as the adenomas increase in size from small to large in the Min/+ mouse.
The mechanism that drives the growth of some colonic adenomas towards malignancy, while permitting others to remain for decades in quiescence, remains unknown. Diets can alter the growth rate of intestinal tumours but it is still unknown whether diets are able to alter the molecular biology of these adenomas in a way that predicts further outcome. To address this issue we fed Min/+ mice with two diets known to lead to different adenoma outcomes: a high-fat control diet (n 15) or a high-fat inulin-enriched (10 % w/w) diet (n 13). To study the effect of diet on cell signalling during adenoma growth, the adenomas of each Min/+ mouse were divided into three size-categories, and the levels of beta-catenin, E-cadherin, cyclin D1 and matrix metalloproteinase-9, which are known to be involved in colon tumorigenesis, were determined. The growth-promoting inulin diet resulted in more large adenomas than the control feeding (P = 0.003) and doubled the total area of the adenomas (P = 0.008). The inulin diet increased the expression of nuclear beta-catenin (P = 0.004) and its target cyclin D1 (P = 0.017) as the adenomas increased in size from small to large, indicating the presence of an accelerated cancerous process. Neither phenomenon was seen in the control group during adenoma growth. Our results suggest that in addition to the number, size, and growth rate of adenomatous polyps, the signalling pattern of the adenomas should also be considered when evaluating preventive dietary strategies.
Misikangas
Marjo
M
Department of Applied Chemistry and Microbiology, Division of Nutrition, University of Helsinki, Finland.
Tanayama
Heidi
H
Rajakangas
Johanna
J
Lindén
Jere
J
Pajari
Anne-Maria
AM
Mutanen
Marja
M
D011125:Adenomatous Polyposis Coli / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism*; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D018450:Disease Progression; D007444:Inulin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism*
D015820:Cadherins; D004041:Dietary Fats; D009363:Neoplasm Proteins; D051176:beta Catenin; D019938:Cyclin D1; D007444:Inulin