{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T06:55:51Z","timestamp":1787986551813,"version":"build-2784847793"},"reference-count":53,"publisher":"National Academy of Sciences","issue":"12","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,6,11]]},"abstract":"<jats:p>\n                    Inactivating mutations of the adenomatous polyposis coli gene (\n                    <jats:italic>APC<\/jats:italic>\n                    ) or activating mutations of the \u03b2-catenin gene (\n                    <jats:italic>CTNNB1<\/jats:italic>\n                    ) initiate colorectal neoplasia. To address the biochemical and physiologic effects of mutant \u03b2-catenin, we disrupted either the mutant or wild-type\n                    <jats:italic>CTNNB1<\/jats:italic>\n                    allele in a human colorectal cancer cell line. Cells with only wild-type \u03b2-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 \u03b2-catenin activity was distinguished primarily by cellular localization and not by protein degradation. Surprisingly, we found mutant \u03b2-catenin bound less well to E-cadherin than did wild-type \u03b2-catenin, and the membranous localization of wild-type and mutant \u03b2-catenin was accordingly distinct. These findings pose several challenges to current models of APC\/\u03b2-catenin function.\n                  <\/jats:p>","DOI":"10.1073\/pnas.082240999","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:46:49Z","timestamp":1027680409000},"page":"8265-8270","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":110,"title":["Targeted inactivation of\n                    <i>CTNNB1<\/i>\n                    reveals unexpected effects of \u03b2-catenin mutation"],"prefix":"10.1073","volume":"99","author":[{"given":"Timothy A.","family":"Chan","sequence":"first","affiliation":[{"name":"The Sidney Kimmel Comprehensive Cancer Center and The Howard Hughes Medical Institute, Johns Hopkins Medical Institutions, 1650 Orleans Street, Baltimore, MD 21231"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenghe","family":"Wang","sequence":"additional","affiliation":[{"name":"The Sidney Kimmel Comprehensive Cancer Center and The Howard Hughes Medical Institute, Johns Hopkins Medical Institutions, 1650 Orleans Street, Baltimore, MD 21231"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long H.","family":"Dang","sequence":"additional","affiliation":[{"name":"The Sidney Kimmel Comprehensive Cancer Center and The Howard Hughes Medical Institute, Johns Hopkins Medical Institutions, 1650 Orleans Street, Baltimore, MD 21231"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert","family":"Vogelstein","sequence":"additional","affiliation":[{"name":"The Sidney Kimmel Comprehensive Cancer Center and The Howard Hughes Medical Institute, Johns Hopkins Medical Institutions, 1650 Orleans Street, Baltimore, MD 21231"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth W.","family":"Kinzler","sequence":"additional","affiliation":[{"name":"The Sidney Kimmel Comprehensive Cancer Center and The Howard Hughes Medical Institute, Johns Hopkins Medical Institutions, 1650 Orleans Street, Baltimore, MD 21231"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2002,6,11]]},"reference":[{"key":"e_1_3_3_1_2","volume-title":"Cancer Facts & Figures","year":"2001","unstructured":"Cancer Facts & Figures (Am. 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