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.
Jawhari
A U
AU
Digestive Diseases Research Centre, St Bartholomew's and the Royal London School of Medicine and Dentistry, Whitechapel, London, UK.
Noda
M
M
Farthing
M J
MJ
Pignatelli
M
M
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