Promotion of adenoma growth by dietary inulin is associated with increase in cyclin D1 and decrease in adhesion proteins in Min/+ mice mucosa.
We have earlier shown that dietary fructo-oligosaccharide inulin enhances adenoma growth in multiple intestinal neoplasia (Min/+) mice. To further explore inulin-induced early biochemical changes in the normal-appearing mucosa, Min/+ mice were fed from the age of 5 weeks to the ages of 8 and 15 weeks a control diet or an inulin-enriched diet (10% w/w). In addition, the wild-type littermates were fed with the same diets until the age of 8 weeks, in order to determine whether similar changes happen both in the wild-type and Min/+ mice. The mucosa without adenomas was collected and fractionated to nuclear, cytosolic and membrane pools. The protein levels of beta-catenin, cyclin D1 and E-cadherin were determined by Western blotting at both time points, and immunohistochemical stainings were done for 8-week-old mice. The promotion of adenoma growth by inulin (week 15, 1.3-fold increase, P=.0004) was associated with accumulation of cytosolic and nuclear beta-catenin, and increased amount of cytosolic cyclin D1 (1.5-fold increase, P=.003) in the normal-appearing mucosa of the Min/+ mice. Furthermore, inulin feeding reduced the membranous pools of beta-catenin and E-cadherin. Also in the wild-type mice the drop in membranous beta-catenin was clear (P=.015), and, moreover, a subset of crypts had enhanced nuclear beta-catenin staining. These data indicate that dietary inulin can already activate in the normal-appearing mucosa beta-catenin signaling, which in the presence of Apc mutation induces adenoma growth and even in the wild-type mice direction of the changes is similar.
Department of Applied Chemistry and Microbiology, Division of Nutrition, P.O. Box 66, 00014 University of Helsinki, Helsinki, Finland.
Marjo
M
Misikangas
Anne-Maria
AM
Pajari
Essi
E
Päivärinta
Marja
M
Mutanen
D000236:Adenoma / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D015820:Cadherins / Q000187:drug effects / Q000378:metabolism; D019938:Cyclin D1 / Q000187:drug effects / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004032:Diet; D005260:Female; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007414:Intestinal Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D007444:Inulin / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D015430:Weight Gain; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D019938:Cyclin D1; D007444:Inulin