IN-VITRO GROWTH-INHIBITION OF NEOPLASTICALLY TRANSFORMED-CELLS BY NONTRANSFORMED CELLS - REQUIREMENT FOR GAP JUNCTIONAL INTERCELLULAR COMMUNICATION

We examined whether the inhibition of neoplastically transformed cell growth by co-cultured non-transformed cells involved gap junctional intercellular communication (GJIC). The growth of poorly communicating (similar to 25-35% dye-coupled cells), Ha-ras and neu oncogene-transformed WB-F344 rat liver epithelial cells was inhibited by coculture with highly communicating (90-95 % dye-coupling), non-transformed WB-F344 cells. Inhibition was dependent upon heterologous cell-cell contact and required that the non-transformed cells were GJIC competent. GJIC-deficient mutant WB-F344 cells did not suppress transformed cell growth. Restoration of mutant cell GJIC by transfection with rat connexin43 cDNA restored growth-inhibiting activity. These results clearly demonstrate a role for GJIC in the inhibition of transformed cell growth by non-transformed cells.