Alteration of beta-catenin expression in colonic epithelial cells of familial adenomatous polyposis patients.
It has been found that beta-catenin, a key regulator of the cadherin-mediated cell adhesion system, forms complexes with adenomatous polyposis coli (APC) tumor suppressor protein, and beta-catenin expression levels are affected by exogenously induced APC protein. The effects of intrinsic APC protein alteration on beta-catenin expression levels and its subcellular localization were examined in colonic epithelia of eight patients with familial adenomatous polyposis. In all eight patients, beta-catenin was immunostained at the membranes of the cell-to-cell borders in normal epithelial cells, whereas the nuclei and cytoplasms stained intensely in addition to the membranes in both adenoma and cancer cells. beta-Catenin expression levels in tumor tissues were over three times higher than those in corresponding normal mucosae of all of the three patients, whose resected specimens were available for quantitative immunoblot analysis. In these three patients, mutant truncated APC proteins were detected and shown to have lost the central region, including a known beta-catenin binding domain. beta-Catenin was not coimmunoprecipitated with these mutant APC proteins in tumor tissues but was able to be coprecipitated with glutathione S-transferase-fused APC protein containing a beta-catenin binding domain. These results suggest that the absence of wild type APC protein affects the subcellular localization and expression levels of beta-catenin in human tissues.
Inomata
M
M
Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.
Ochiai
A
A
Akimoto
S
S
Kitano
S
S
Hirohashi
S
S
D011125:Adenomatous Polyposis Coli / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D015534:Trans-Activators; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin