Role of protein kinase C in the deficient gap junctional intercellular communication of K-ras-transformed murine lung epithelial cells.
BACKGROUND
Protein kinase C (PKC) activity is increased and gap junctional intercellular communication (GJIC) is decreased frequently in Ras-transformed cells. We investigated the roles of Ras and PKC in the deficient gap junctional intercellular communication (GJIC) of K-ras-transformed E9 mouse lung carcinoma cells.


METHODS
GJIC was measured by fluorescent dye microinjection. Ras activity was blocked with lovastatin or a K-ras antisense oligonucleotide. PKC activity was inhibited with GF 109203X or apigenin or was downregulated by overnight treatment with 12-O-tetradecanoylphorbol-13-acetate. The content and phosphorylation of the gap junction protein, connexin43 (Cx43), was assessed by Western blot.


RESULTS
E9 cell GJIC was increased two-three fold by lovastatin, the K-ras antisense oligonucleotide, and PKC inhibition/downregulation. Cx43 content and phosphorylation were unchanged, however.


CONCLUSIONS
Oncogenic Ras blocks GJIC in E9 cells through a PKC-dependent mechanism, but this does not directly involve Cx43 expression or phosphorylation.
Cesen-Cummings
K
K
Department of Pathology, Medical College of Ohio, Toledo 43614, USA.
Warner
K A
KA
Ruch
R J
RJ
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D002450:Cell Communication / Q000502:physiology*; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D020843:Chamomile; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells; D005419:Flavonoids / Q000494:pharmacology; D017629:Gap Junctions / Q000502:physiology*; D011905:Genes, ras / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D008148:Lovastatin / Q000494:pharmacology; D008168:Lung; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D008301:Maleimides / Q000494:pharmacology; D051379:Mice; D009822:Oils, Volatile / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010766:Phosphorylation; D010946:Plants, Medicinal; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D018031:Connexin 43; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007211:Indoles; D008301:Maleimides; D009822:Oils, Volatile; D016376:Oligonucleotides, Antisense; D008148:Lovastatin; D011493:Protein Kinase C; C070515:bisindolylmaleimide I; D013755:Tetradecanoylphorbol Acetate