Promotion of intestinal tumor formation by inulin is associated with an accumulation of cytosolic beta-catenin in Min mice.
Inulin, polydisperse beta (2-1) fructan, has been suggested to protect against colon carcinogenesis and is currently used in a number of food applications. However, the data regarding the role of inulin in intestinal carcinogenesis remains controversial since the results of our previous study suggested that inulin promotes intestinal tumor formation in Min mice, an animal model for intestinal cancer with a mutation in the Apc tumor suppressor gene (Carcinogenesis 2000;21:1167-73). In our present study, we further examined the effects of inulin on intestinal tumor formation in Min mice by carefully analyzing beta-catenin expression and cellular localization at 3 different time points during the tumorigenic process. Min mice were fed a high-fat inulin-enriched (10% w/w) diet or the high-fat diet without any added fiber from the age of 6 weeks to the ages of 9, 12 or 15 weeks. The results showed that inulin significantly increased the number (by 20%) and especially the size (by 44%) of adenomas in the small intestine. At week 15, the promotion of tumor development was accompanied by an accumulation of cytosolic beta-catenin in the adenoma tissue. In the normal appearing mucosa, levels of membrane beta-catenin and PCNA were reduced in the inulin-fed mice, possibly indicating impaired enterocyte migration. These data do not support the earlier suggestions on the cancer preventive effects of inulin and emphasize the need for further research and evaluation where health claims for inulin are concerned.
Pajari
Anne-Maria
AM
Department of Applied Chemistry and Microbiology, Division of Nutrition, University of Helsinki, Helsinki, Finland.
Rajakangas
Johanna
J
Päivärinta
Essi
E
Kosma
Veli-Matti
VM
Rafter
Joseph
J
Mutanen
Marja
M
D000236:Adenoma / Q000139:chemically induced* / Q000378:metabolism; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002467:Cell Nucleus / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D005260:Female; D007414:Intestinal Neoplasms / Q000139:chemically induced* / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D007444:Inulin / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D002273:Carcinogens; D003598:Cytoskeletal Proteins; D018809:Proliferating Cell Nuclear Antigen; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; D007444:Inulin