Role of β-Catenin During Early Colorectal and Hepatic Carcinogenesis

Abstract

β-Catenin has been identified as an oncogene in several tumors including colorectal and hepatocellular carcinomas. The β-catenin gene is activated by interstitial deletions involving exon 3 in 3% of colorectal cancers in the Japanese population, by missense mutations in critical serine/threonine residues including exon 3 in 16% of colorectal cancers in Caucasians, and by missense mutations or interstitial deletions in 19%–26% of hepatocellular carcinomas. The type and frequency of the mutation of this gene in colorectal adenomas in Japanese and Caucasians are similar to those in colorectal cancers in each population. As for hepatic tumors, expression of ß-catenin correlates with its accumulation in the cytoplasm and nuclei, which implies activation of the Wnt/Wingless signal transduction pathway in adenomatous hyperplasias and for each differentiation grade of hepatocellular carcinomas with similar frequency. In conclusion, activation of the β-catenin gene by interstitial deletions or missense mutations in the Japanese and Caucasian populations, respectively, may be less frequent than alterations of the adenomatous polyposis coli (APC) gene, but it may be an early event in colorectal tumorigenesis that is equivalent to APC gene alterations. The Wnt/Wingless signal transduction pathway may be activated during early hepatic carcinogenesis.