beta-catenin expression in primary and metastatic colorectal carcinoma

Int J Cancer. 1999 Aug 12;82(4):504-11. doi: 10.1002/(sici)1097-0215(19990812)82:4<504::aid-ijc6>;2-6.


beta-catenin plays a fundamental role in the regulation of the E-cadherin-catenin cell adhesion complex. It also functions in growth signalling events, independently of the cadherin-catenin complex, and these signalling pathways are disturbed in colorectal cancer. Mutations in either the APC or beta-catenin genes in colorectal cancer cells result in up-regulation of protein expression and subsequent cytoplasmic and nuclear distribution of beta-catenin. In this study, we examined beta-catenin expression in 47 primary colorectal tumors and the corresponding liver metastases. Immunohistochemical studies demonstrated loss of membranous beta-catenin expression in 26% of primary tumors and 60% of liver metastases and a concomitant increase in cytoplasmic and nuclear staining. Widespread nuclear expression of beta-catenin was found in 64% of primary tumors and 21% of liver metastases. No associations were found between any form of beta-catenin expression and either tumor stage or tumor grade. Cellular distribution of beta-catenin was also examined by detergent extraction and Western blot analysis in 16 primary tumors and 23 liver metastases. This analysis showed that most tumors demonstrated reduced beta-catenin in the cytoskeletal fraction and increased beta-catenin in the cytosolic fraction. Furthermore, 3 liver metastases were found to contain a truncated beta-catenin protein of approximately M(r) 80,000. Immunoprecipitation studies showed that the truncated beta-catenin proteins only bound weakly to E-cadherin and beta-catenin compared with non-truncated beta-catenin. These results demonstrate gross alterations in the cellular distribution of beta-catenin in primary colorectal cancers with metastatic potential, as well as in the metastatic tumors. These changes may be the consequence of APC or beta-catenin gene mutations, or possibly result from a post-translational modification of the E-cadherin-catenin complex.

MeSH terms

  • Adult
  • Aged
  • Blotting, Western
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • Cytoskeletal Proteins / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / secondary
  • Male
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Rectal Neoplasms / metabolism*
  • Rectal Neoplasms / pathology
  • Trans-Activators*
  • beta Catenin


  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Neoplasm Proteins
  • Trans-Activators
  • beta Catenin