title: Nuclear translocation of beta-catenin in hereditary and carcinogen-induced intestinal adenomas.
abstract: The physical interaction between beta-catenin and the adenomatous polyposis coli (APC) gene, and the ability of APC to regulate cytoplasmic levels of beta-catenin suggest a role for beta-catenin in colorectal carcinogenesis. In this study, we found that beta-catenin immunoreactivity was detected exclusively in the cell membrane and cytoplasm of morphologically normal intestinal epithelial cells with predominant distribution in the differentiated nonproliferative cell population. In contrast, beta-catenin was localized predominantly in the nucleus of adenomas from Min/+ mice and transgenic mice expressing a mutant truncated form of the APC gene (Apc(delta716) mice). Beta-catenin was expressed predominantly at the cell membrane and cytoplasm of the nontransformed rat intestinal epithelial (RIE-1) cells in culture, whereas predominantly nuclear localization of beta-catenin was observed in the human colon cancer cell line SW480. In the azoxymethane (AOM) treated rats, overexpression and nuclear localization of beta-catenin was observed in all adenomas. Previous studies have indicated the incidence of APC mutations amongst AOM-induced tumors to be 15% or less. These results demonstrate that nuclear localization of beta-catenin is a common event in colorectal tumorigenesis.
authors.affiliation: Department of Surgery, The Vanderbilt Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: H
authors.initials: H
authors.lastname: Sheng
authors.forename: J
authors.initials: J
authors.lastname: Shao
authors.forename: C S
authors.initials: CS
authors.lastname: Williams
authors.forename: M A
authors.initials: MA
authors.lastname: Pereira
authors.forename: M M
authors.initials: MM
authors.lastname: Taketo
authors.forename: M
authors.initials: M
authors.lastname: Oshima
authors.forename: A B
authors.initials: AB
authors.lastname: Reynolds
authors.forename: M K
authors.initials: MK
authors.lastname: Washington
authors.forename: R N
authors.initials: RN
authors.lastname: DuBois
authors.forename: R D
authors.initials: RD
authors.lastname: Beauchamp
mesh_terms: D000236:Adenoma / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001397:Azoxymethane / Q000633:toxicity*; D001692:Biological Transport; D002273:Carcinogens / Q000633:toxicity*; D002467:Cell Nucleus / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D017491:Genes, APC; D006801:Humans; D007414:Intestinal Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D002273:Carcinogens; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D001397:Azoxymethane