Promotion of adenoma growth by dietary inulin is associated with increase in cyclin D1 and decrease in adhesion proteins in Min/+ mice mucosa

J Nutr Biochem. 2005 Jul;16(7):402-9. doi: 10.1016/j.jnutbio.2005.01.013.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / chemically induced
  • Adenoma / metabolism
  • Adenoma / pathology*
  • Animals
  • Cadherins / drug effects
  • Cadherins / metabolism
  • Cyclin D1 / drug effects
  • Cyclin D1 / metabolism*
  • Cytoskeletal Proteins / metabolism
  • Cytosol / metabolism
  • Diet*
  • Female
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism*
  • Intestinal Neoplasms / chemically induced
  • Intestinal Neoplasms / metabolism
  • Intestinal Neoplasms / pathology*
  • Inulin / adverse effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Signal Transduction
  • Trans-Activators / metabolism
  • Weight Gain
  • beta Catenin

Substances

  • CTNNB1 protein, mouse
  • Cadherins
  • Cytoskeletal Proteins
  • Trans-Activators
  • beta Catenin
  • Cyclin D1
  • Inulin