Further upregulation of beta-catenin/Tcf transcription is involved in the development of macroscopic tumors in the colon of ApcMin/+ mice

Carcinogenesis. 2008 Mar;29(3):666-72. doi: 10.1093/carcin/bgn001. Epub 2008 Jan 19.


Apc(Min/+) mouse, a mouse model for human familial adenomatosis polyposis, contains a truncating mutation in the Apc gene and spontaneously develops intestinal tumors. Our previous study revealed two distinct stages of tumorigenesis in the colon of Apc(Min/+) mouse: microadenomas and macroscopic tumors. Microadenomas already have lost their remaining allele of the Apc and all microadenomas show accumulation of beta-catenin, indicating that activation of the canonical Wnt pathway is an initiating event in the tumorigenesis. This study shows that expression of nuclear beta-catenin in macroscopic tumors is further upregulated in comparison with that in microadenomas. Furthermore, transcriptional activity of beta-catenin/T-cell factor (Tcf) signaling, assessed using beta-catenin/Tcf reporter transgenic mice, is higher in the macroscopic tumors than that in microadenomas. In addition, the expression level of Dickkopf-1, which is known to be a negative modifier of the canonical Wnt pathway, was reduced only in colon tumors. These results suggest that activation of beta-catenin/Tcf transcription plays a role not only in the initiation stage but also in the promotion stage of colon carcinogenesis in Apc(Min/+) mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology*
  • Flow Cytometry
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins / genetics
  • Mice
  • Mice, Mutant Strains
  • Reverse Transcriptase Polymerase Chain Reaction
  • T Cell Transcription Factor 1 / genetics*
  • Transcription, Genetic*
  • Up-Regulation*
  • Wnt Proteins / antagonists & inhibitors
  • beta Catenin / genetics*


  • Dkk1 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • T Cell Transcription Factor 1
  • Wnt Proteins
  • beta Catenin