Targeted inactivation of CTNNB1 reveals unexpected effects of beta-catenin mutation.

Inactivating mutations of the adenomatous polyposis coli gene (APC) or activating mutations of the beta-catenin gene (CTNNB1) initiate colorectal neoplasia. To address the biochemical and physiologic effects of mutant beta-catenin, we disrupted either the mutant or wild-type CTNNB1 allele in a human colorectal cancer cell line. Cells with only wild-type ...
beta-catenin had decreased colony-forming ability when plated at low density, although their growth was similar to that of parental cells when passaged under routine conditions. Immunohistochemistry and cell-fractionation studies suggested that mutant beta-catenin activity was distinguished primarily by cellular localization and not by protein degradation. Surprisingly, we found mutant beta-catenin bound less well to E-cadherin than did wild-type beta-catenin, and the membranous localization of wild-type and mutant beta-catenin was accordingly distinct. These findings pose several challenges to current models of APC/beta-catenin function.
Mesh Terms:
Chromosomes, Artificial, Bacterial, Colorectal Neoplasms, Cytoskeletal Proteins, Gene Deletion, Gene Expression Regulation, Neoplastic, Genes, APC, Heterozygote, Humans, Introns, Mutagenesis, RNA Processing, Post-Transcriptional, Recombinant Proteins, Trans-Activators, Transcription, Genetic, Transfection, Tumor Cells, Cultured, Tumor Stem Cell Assay, beta Catenin
Proc Natl Acad Sci U S A
Date: Jun. 11, 2002
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