Targeted inactivation of CTNNB1 reveals unexpected effects of β-catenin mutation

Timothy A. Chan, Zhenghe Wang, Long H. Dang, Bert Vogelstein, Kenneth W. Kinzler

Research output: Contribution to journalArticlepeer-review

Abstract

Inactivating mutations of the adenomatous polyposis coli gene (APC) or activating mutations of the β-catenin gene (CTNNB1) initiate colorectal neoplasia. To address the biochemical and physiologic effects of mutant β-catenin, we disrupted either the mutant or wild-type CTNNB1 allele in a human colorectal cancer cell line. Cells with only wild-type β-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 β-catenin activity was distinguished primarily by cellular localization and not by protein degradation. Surprisingly, we found mutant β-catenin bound less well to Ecadherin than did wild-type β-catenin, and the membranous localization of wild-type and mutant β-catenin was accordingly distinct. These findings pose several challenges to current models of APC/β-catenin function.

Original languageEnglish (US)
Pages (from-to)8265-8270
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number12
DOIs
StatePublished - Jun 11 2002

ASJC Scopus subject areas

  • General

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