Subcellular localization of beta-catenin and APC proteins in colorectal preneoplastic and neoplastic lesions

Cancer Lett. 2006 Sep 28;241(2):203-12. doi: 10.1016/j.canlet.2005.10.011. Epub 2005 Nov 17.


Adenomatous polyposis coli (APC) is a tumor suppressor gene whose main function is the destabilization of beta-catenin, a key effector of the Wnt signaling pathway. This gene is defective in familial adenomatous polyposis (FAP), a dominantly inherited disease, but inactivation of APC has been reported also in most sporadic colorectal tumors and it is considered an early event in colorectal tumorigenesis. The aim of the present study was to evaluate the intracellular ultrastructural distribution of beta-catenin and APC proteins in epithelial cells of normal colorectal mucosa, aberrant crypt foci (ACF, an early premalignant lesion) and cancer. We used the immunogold electron microscopic method to identify both proteins. Normal colonic epithelial cells showed a strong membranous expression of beta-catenin and lacked cytoplasmic and nuclear expression. Normal cells showed APC localization pattern characterized by diffuse nuclear expression and along the plasma membrane. In ACF and in carcinoma an absent or reduced membranous expression of beta-catenin was associated with an increased nuclear and cytoplasmatic expression. In aberrant crypt foci and carcinoma, APC was evident inside the nucleus and at the level of cell-cell junctions, but it was decreased in the cytoplasm. This method allowed the accurate localization of proteins of the Wnt signaling pathway in the early steps of colorectal carcinogenesis. The similar pattern of subcellular distribution of APC and beta-catenin in dysplastic ACF and colorectal cancer suggests that ACF are precursor lesions of sporadic and FAP-associated colorectal carcinoma.

Publication types

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

MeSH terms

  • Adenomatous Polyposis Coli / pathology
  • Adenomatous Polyposis Coli Protein / metabolism*
  • Cell Nucleus / metabolism
  • Cell Nucleus / ultrastructure
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Cytoplasm / metabolism
  • Cytoplasm / ultrastructure
  • Humans
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / ultrastructure
  • Microscopy, Immunoelectron
  • Precancerous Conditions / metabolism*
  • Precancerous Conditions / pathology
  • Subcellular Fractions
  • beta Catenin / metabolism*


  • Adenomatous Polyposis Coli Protein
  • beta Catenin