Abnormal expression and function of the E-cadherin-catenin complex in gastric carcinoma cell lines.

Abstract

Dysfunction of the cadherin–catenin complex, a key component of adherens junctions, is thought to confer invasive potential to cells. The aim of this study is to examine the expression and function of the E-cadherin/catenin complex in gastric carcinoma cell lines. Expression of E-cadherin, α, β and γ-catenin and p120ctn, and of the adenomatous polyposis coli protein (APC), together with function of the cadherin–catenin complex was examined in a panel of gastric carcinoma cell lines, using immunocytochemistry, Western blotting and a cell–cell aggregation assay. Protein interactions were examined by sequential immunoprecipitation and immunoblotting with antibodies to E-cadherin, α, β and γ-catenin, p120ctn and APC. Abnormalities of E-cadherin, α- and β-catenin expression, were associated with disturbance of E-cadherin–catenin complex composition, loss of membranous localization and loss of calcium-dependent aggregation in six gastric carcinoma cell lines. APC protein expression and interaction with β-catenin was preserved in five cell lines. We demonstrate frequent abnormalities of expression and function of E-cadherin and catenins, and associated disturbance of E-cadherin-mediated intercellular adhesion in gastric carcinoma cell lines. These findings support the tumour suppressor role of the E-cadherin and its contribution to the development and progression of the neoplastic phenotype in gastric carcinoma. © 1999 Cancer Research Campaign