Ras is involved in gap junction closure in proliferating fibroblasts or preadipocytes but not in differentiated adipocytes

A decrease in gap junctional, intercellular communication (GJIC) has been associated with cells neoplastically transformed by a variety of factors, To investigate the role of the Ras oncogene product in gap junction function, a panel of murine C3H10T 1/2 (10T 1/2) fibroblasts was constructed in which the levels of ras gene expression could be effectively up- or down-regulated, Intercellular communication was measured using a novel technique of in situ electroporation of adherent cells on a partly conductive slide. The introduction of increasing amounts of activated Ras(leu61) in mouse 10T 1/2 fibroblasts proportionally reduced GJIC, while the downregulation of endogenous c-ras gene expression increased junctional permeability, These results indicate that Ras plays an important role in the junction closure pathway leading to the proliferation of normal cells. However, differentiation of c-Ras-deficient preadipocytes entirely abolished their initially extensive GJIC, indicating that junction closure in response to adipocytic differentiation is independent of Ras.