Abnormal expression and function of the E-cadherin-catenin complex in gastric carcinoma cell lines.
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, alpha, beta and gamma-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, alpha, beta and gamma-catenin, p120ctn and APC. Abnormalities of E-cadherin, alpha- and beta-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 beta-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.
Digestive Diseases Research Centre, St Bartholomew's and the Royal London School of Medicine and Dentistry, Whitechapel, London, UK.
A U
AU
Jawhari
M
M
Noda
M J
MJ
Farthing
M
M
Pignatelli
D000818:Animals; D015820:Cadherins / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion / Q000502:physiology; D002449:Cell Aggregation / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D051178:alpha Catenin; D051176:beta Catenin
C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D015820:Cadherins; C495272:Ctnna1 protein, mouse; D003598:Cytoskeletal Proteins; D046911:Macromolecular Substances; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin