title: Induction of mutual stabilization and retardation of tumor growth by coexpression of plakoglobin and E-cadherin in mouse skin spindle carcinoma cells.
abstract: The influence of plakoglobin on the phenotype and tumorigenicity of murine spindle carcinoma cells was analyzed by stable transfection of plakoglobin cDNA in the presence or absence of E-cadherin expression. In either situation, overexpression of plakoglobin was unable to modify the fibroblastic phenotype or to completely suppress the tumorigenic behavior of the spindle cells, but a moderate reduction in the growth rate of the tumors was induced by plakoglobin and was further enhanced by E-cadherin. Coexpression of E-cadherin and plakoglobin induced a mutual stabilization, increasing the half-life of both molecules in the double transfectants more than 5- and 30-fold, respectively, with a turnover rate similar to that observed in control keratinocytes. The stabilization of E-cadherin, as well as that of plakoglobin, was maintained in the tumors induced by the double transfectants, in contrast to the unstable expression of E-cadherin observed in tumors induced in plakoglobin-deficient cells. The E-cadherin/catenin complexes present in the double transfectants were functional in calcium-dependent aggregation assays and similar in composition to those of control keratinocytes. However, most of the components of the complexes of the transfectants were solubilized by non-ionic detergents, indicating a weak interaction with the actin cytoskeleton. These results indicated that restoration of E-cadherin/catenin complexes was not sufficient to induce the transition of the fibroblastic cells to an epithelial phenotype or to completely suppress the tumorigenicity of mouse skin spindle carcinoma cells.
authors.affiliation: Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas, and Departamento de Bioquímica, Universidad Autónoma de Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Lozano
authors.forename: A
authors.initials: A
authors.lastname: Cano
mesh_terms: D000818:Animals; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002118:Calcium / Q000494:pharmacology; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018076:DNA, Complementary / Q000235:genetics; D051180:Desmoplakins; D003902:Detergents / Q000494:pharmacology; D018450:Disease Progression; D005347:Fibroblasts / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006207:Half-Life; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D046911:Macromolecular Substances; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010641:Phenotype; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D051185:gamma Catenin
chemical_list: D015820:Cadherins; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D051180:Desmoplakins; D003902:Detergents; D046911:Macromolecular Substances; D051185:gamma Catenin; D002118:Calcium