Induction of mutual stabilization and retardation of tumor growth by coexpression of plakoglobin and E-cadherin in mouse skin spindle carcinoma cells.

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.