期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：12
页码：8265-8270
DOI：10.1073/pnas.082240999
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
