Nuclear translocation of beta-catenin in hereditary and carcinogen-induced intestinal adenomas.
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.
Sheng
H
H
Department of Surgery, The Vanderbilt Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Shao
J
J
Williams
C S
CS
Pereira
M A
MA
Taketo
M M
MM
Oshima
M
M
Reynolds
A B
AB
Washington
M K
MK
DuBois
R N
RN
Beauchamp
R D
RD
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
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