EXPRESSION OF E-CADHERIN OR P-CADHERIN IS NOT SUFFICIENT TO MODIFY THE MORPHOLOGY AND THE TUMORIGENIC BEHAVIOR OF MURINE SPINDLE CARCINOMA-CELLS - POSSIBLE INVOLVEMENT OF PLAKOGLOBIN

Transfection of E- and P-cadherin CDNA has been carried out in murine spindle carcinoma cells previously shown to be deficient in both cadhe rins (Navarro et al., J. Cell Biol. 115, 517-533, 1991). High levels o f expression of E- or P-cadherin do not significantly affect the fibro blastic morphology of the parental spindle cells. In addition, the tum origenic behavior of these highly malignant cells is not influenced by the ectopic expression of either cadherin. Nevertheless, a fraction o f the exogenous cadherins is able to associate to detergent-insoluble components of the transfectant cells, and the expression of the exogen ous E-cadherin confers Ca2+-dependent aggregation on the spindle trans fectants in an in vitro assay. Immunoprecipitation analysis of the cad herin-catenin complex of the transfectants revealed that the ectopic E -cadherin associates with the alpha- and beta-catenin proteins. Howeve r, the gamma-catenin/plakoglobin component could not be detected in th e E-cadherin immunocomplexes of the spindle transfectant cells, in con trast to the epithelial cells where the three catenins appeared to be associated with E-cadherin. The lack of association of gamma-catenin i s correlated with very low levels of plakoglobin in whole cell extract s of the parental spindle cells. These results indicate that the assoc iation of E-cadherin with the alpha- and beta-catenin components is no t sufficient to promote a fibroblastoid-epithelial conversion of highl y malignant spindle cells. The presence of plakoglobin could be requir ed for the proper organization of E-cadherin in the transfectant cells in order to acquire an epithelioid phenotype.