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. 1998 Feb;77(4):605–613. doi: 10.1038/bjc.1998.97

Aberrant expression and phosphorylation of beta-catenin in human colorectal cancer.

T Takayama 1, H Shiozaki 1, Y Doki 1, H Oka 1, M Inoue 1, M Yamamoto 1, S Tamura 1, S Shibamoto 1, F Ito 1, M Monden 1
PMCID: PMC2149924  PMID: 9484818

Abstract

The cytoplasmic domain of cadherins is known to associate with the intracellular proteins, catenins, which link cadherins to the actin-based cytoskeleton. In this study, we immunohistochemically investigated the expression of beta-catenin as well as E-cadherin and alpha-catenin in 86 human colorectal cancers, and we analysed their coexpression pattern and relationship to clinicopathological factors. In cancerous tissues, the frequency of reduced expression of beta-catenin (28 of 86, 33%) was similar to that of E-cadherin (19 of 86, 22%), but less than that of alpha-catenin (47 of 86, 55%). All three molecules were expressed strongly, as was the normal epithelium, in 36 cases (42%), whereas the rest (50 cases, 58%) showed reduction in one of the molecules. The reduction of beta-catenin expression was significantly correlated with dedifferentiation, Duke's stage, lymph node metastasis and liver metastasis. Next, we examined tyrosine phosphorylation in the protein complex immunoprecipitated with E-cadherin, as E-cadherin function is down-regulated by receptor-type tyrosine kinase in vitro. It was of interest that up-regulation of tyrosine phosphorylation of beta-catenin was more frequently observed in cancerous tissues than in the matching normal mucosa. These results suggest that beta-catenin may have important regulatory roles within an E-cadherin-mediated adhesion system in human colorectal cancers.

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