Nuclear translocation of beta-catenin in hereditary and carcinogen- induced intestinal adenomas

The physical interaction between beta-catenin and the adenomatous polyposiscoli (APC) gene, and the ability of APC to regulate cytoplasmic levels ofbeta-catenin suggest a role for beta-catenin in colorectal carcinogenesis.In this study, we found that beta-catenin immunoreactivity was detectedexclusively in the cell membrane and cytoplasm of morphologically normalintestinal epithelial cells with predominant distribution in thedifferentiated nonproliferative cell population. In contrast, beta-cateninwas localized predominantly in the nucleus of adenomas from Min/+ mice andtransgenic mice expressing a mutant truncated form of the APC gene(Apc(delta716) mice). Beta- catenin was expressed predominantly at the cellmembrane and cytoplasm of the nontransformed rat intestinal epithelial(RIE-1) cells in culture, whereas predominantly nuclear localization ofbeta-catenin was observed in the human colon cancer cell line SW480. In theazoxymethane (AOM) treated rats, overexpression and nuclear localization ofbeta- catenin was observed in all adenomas. Previous studies have indicatedthe incidence of APC mutations amongst AOM-induced tumors to be 15% orless. These results demonstrate that nuclear localization of beta- cateninis a common event in colorectal tumorigenesis.