In vitro growth inhibition of neoplastically transformed cells by non-transformed 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 (approximately 25-35% dye-coupled cells), Ha-ras and neu oncogene-transformed WB-F344 rat liver epithelial cells was inhibited by co-culture 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.
Esinduy
C B
CB
Department of Pathology, Medical College of Ohio, Toledo 43699.
Chang
C C
CC
Trosko
J E
JE
Ruch
R J
RJ
D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004396:Coloring Agents; D018031:Connexin 43 / Q000032:analysis; D004847:Epithelial Cells; D017629:Gap Junctions / Q000502:physiology*; D018734:Genes, erbB-2; D011905:Genes, ras; D008099:Liver / Q000166:cytology; D008845:Microinjections; D051381:Rats; D011916:Rats, Inbred F344
D004396:Coloring Agents; D018031:Connexin 43