Evaluation of the malignant potential of aberrant crypt foci by immunohistochemical staining for beta-catenin in inflammation-induced rat colon carcinogenesis

Int J Mol Med. 2002 Apr;9(4):353-8.


We previously showed that colitis enhanced the development of cancer and aberrant crypt foci (ACF) in 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in Fischer 344 rats. In this study, we examined the effect of two different anti-inflammatory drugs [non-steroidal anti-inflammatory drugs (NSAIDs: Fenbufen) and a platelet activating factor-receptor antagonist (PAF-RA)] on the inflammation-induced rat colon carcinogenesis. Furthermore, we examined the expression and the localization of beta-catenin protein, and the proliferating cell nuclear antigen (PCNA)-labeling index (LI) in ACF and cancer. PAF-RA significantly decreased the incidence of ACF in the rats (p<0.05), but Fenbufen did not affect the incidence of ACF and cancer. In most of the ACF (91%), beta-catenin was localized at the cell membrane like in normal colon epithelium. In about 9% of the ACF, beta-catenin was overexpressed not only on the cell membrane but also in the cytoplasm. In all of the cancer cells, beta-catenin was overexpressed in the nucleus. When we compared the PCNA-LI in the ACF showing normal beta-catenin expression pattern with that in the ACF showing abnormal beta-catenin expression pattern (overexpression in cytoplasm), there was no significant difference of the PCNA-LI in these two different types of ACF. These findings suggest that immunohistochemical staining of ACF for beta-catenin can evaluate the malignant potential of ACF, and that PAF-RA can be used for preventing the development of ACF in inflammation-induced carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Biomarkers, Tumor*
  • Cell Division
  • Colitis, Ulcerative / complications
  • Colitis, Ulcerative / drug therapy
  • Colitis, Ulcerative / metabolism
  • Colitis, Ulcerative / pathology
  • Colonic Neoplasms / chemically induced*
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology*
  • Cytoskeletal Proteins / metabolism*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology*
  • Male
  • Phenylbutyrates / pharmacology
  • Platelet Membrane Glycoproteins / antagonists & inhibitors
  • Rats
  • Rats, Inbred F344
  • Receptors, Cell Surface*
  • Receptors, G-Protein-Coupled*
  • Trans-Activators*
  • beta Catenin


  • Anti-Inflammatory Agents, Non-Steroidal
  • Biomarkers, Tumor
  • Ctnnb1 protein, rat
  • Cytoskeletal Proteins
  • Phenylbutyrates
  • Platelet Membrane Glycoproteins
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Trans-Activators
  • beta Catenin
  • platelet activating factor receptor
  • fenbufen