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Altered expression and mutation of β‐catenin gene in gastric carcinomas and cell lines
Author(s) -
Woo Dong Kyun,
Kim Hee Sung,
Lee Hye Seung,
Kang Young Hwa,
Yang Han Kwang,
Kim Woo Ho
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20010320)95:2<108::aid-ijc1019>3.0.co;2-#
Subject(s) - catenin , mutation , gene , cancer research , biology , gene expression , cell culture , beta catenin , cell , pathology , genetics , medicine , wnt signaling pathway
β‐Catenin serves not only as a structural component of the E‐cadherin‐mediated cell–cell adhesion system, but also as a signaling molecule of the Wnt/wingless pathway. Deregulated expression of β‐catenin and mutations of the gene have been identified in a number of human malignancies. To determine the role of β‐catenin defects in stomach cancer, we investigated β‐catenin exon 3 mutations and altered protein expression in 77 primary gastric carcinomas and 11 cell lines. In addition, the immunohistochemical expression pattern of β‐catenin in 303 consecutive gastric cancers was determined and their relationships with clinicopathologic features and patient outcome were investigated. This study revealed 5% (4 of 77) tumors and 27% (3 of 11) cell lines with β‐catenin gene alteration, 6 missense mutations, and 1 interstitial deletion. These genetic changes were shown to correlate closely with nuclear localization of the protein ( p = 0.001). In an immunohistochemical analysis, abnormal expressions of β‐catenin, such as nuclear accumulation and loss of membranous distribution, were detected in 27% (81 of 303) of tumors overall. These altered β‐catenin expressions were more commonly observed in 37% (58 of 158) diffuse type gastric carcinomas ( p < 0.001). Loss of membranous β‐catenin staining was associated with poor survival ( p = 0.045). In conclusion, our results demonstrate that β‐catenin mutations are common in gastric cancer cell lines but occur infrequently in gastric carcinoma tissues. These mutations are one of the causes of the nuclear accumulation of β‐catenin. Frequent abnormalities of β‐catenin expression in gastric carcinoma support the idea that both structural and signaling functions of the protein play a critical role in gastric carcinogenesis. © 2001 Wiley‐Liss, Inc.