Tumor formation is correlated with expression of beta-catenin-accumulated crypts in azoxymethane-induced colon carcinogenesis in mice

Cancer Sci. 2004 Apr;95(4):316-20. doi: 10.1111/j.1349-7006.2004.tb03209.x.


We have reported that beta-catenin-accumulated crypts (BCAC) are independent of aberrant crypt foci (ACF) in the colonic mucosa of rats exposed to colorectal carcinogens, and we suggested that they may be premalignant lesions. In the present study, we performed a comparative study on the formation of the two types of early-appearing lesions (BCAC and ACF), and tumors of the colon in two mouse strains with different susceptibility to azoxymethane (AOM). SWR/J mice are known to be relatively susceptible to AOM, whereas AKR/J mice are reported to be virtually resistant. Both AKR/J and SWR/J mice, 6 weeks old, received subcutaneous injections of AOM (15 mg/kg body weight) once a week for 3 weeks, and were sacrificed at 16 and 41 weeks of age. Colons of the animals sacrificed at 16 and 41 weeks of age were processed to examine expression of the early-appearing lesions and neoplasms. Although AKR/J mice had a lower incidence of colonic tumors than SWR/J mice did, AKR/J mice showed a similar frequency of ACF to that in SWR/J mice. In both strains, ACF were detected at high frequency in the proximal colon, whereas tumors developed mainly in the distal colon. Importantly, the incidence of BCAC in SWR/J mice was significantly higher than that in AKR/J mice, and the highest frequency was observed in the distal segments of the colon. These results support the idea that BCAC are a reliable surrogate endpoint for colon carcinogenesis in mice.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / chemically induced*
  • Adenocarcinoma / chemistry
  • Adenocarcinoma / pathology
  • Adenoma / chemically induced*
  • Adenoma / chemistry
  • Adenoma / pathology
  • Animals
  • Azoxymethane / toxicity*
  • Biomarkers, Tumor / analysis*
  • Carcinogens / toxicity*
  • Colonic Neoplasms / chemically induced*
  • Colonic Neoplasms / chemistry
  • Colonic Neoplasms / pathology
  • Cytoskeletal Proteins / analysis*
  • Genetic Predisposition to Disease
  • Intestinal Mucosa / chemistry
  • Intestinal Mucosa / pathology*
  • Mice
  • Mice, Inbred AKR
  • Mucins / analysis
  • Neoplasm Proteins / analysis*
  • Specific Pathogen-Free Organisms
  • Trans-Activators / analysis*
  • beta Catenin


  • Biomarkers, Tumor
  • CTNNB1 protein, mouse
  • Carcinogens
  • Cytoskeletal Proteins
  • Mucins
  • Neoplasm Proteins
  • Trans-Activators
  • beta Catenin
  • Azoxymethane