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 mu rine spindle carcinoma cells was analyzed by stable transfection of pl akoglobin 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 b ehavior of the spindle cells, but a moderate reduction in the growth r ate of the tumors was induced by plakoglobin and was further enhanced by E-cadherin, Coexpression of E-cadherin and plakoglobin induced a mu tual stabilization, increasing the ha If-life of both molecules in the double transfectants more than 5- and 30-fold, respectively, with a t urnover rate similar to that observed in control keratinocytes. The st abilization of E-cadherin, as well as that of plakoglobin, was maintai ned in the tumors induced by the double transfectants, in contrast to the unstable expression of E-cadherin observed in tumors induced in pl akoglobin-deficient cells. The E-cadherin/catenin complexes present in the double transfectants were functional in calcium-dependent aggrega tion assays and similar in composition to those of control keratinocyt es. However, most of the components of the complexes of the transfecta nts were solubilized by non-ionic detergents, indicating a weak intera ction with the actin cytoskeleton. These results indicated that restor ation 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 carcinom a cells. (C) 1998 Wiley-Liss, Inc.