Protein kinase Calpha promotes apoptotic cell death in gastric cancer cells depending upon loss of anchorage.
Disruption of interactions between epithelial cells and extracellular matrix proteins leads to apoptosis of the cells, a phenomenon termed anoikis. Anoikis seems to play important roles in control of cellular positioning and inhibition of inappropriate cell growth. Here we found that a protein kinase C (PKC) activator phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) promoted cell death in human gastric cancer cell lines MKN45 and MKN74 only when they lost anchorage. Loss of anchorage slightly increased enzymatic activity of PKCalpha, and an addition of TPA promoted cell death with further increase of PKCalpha activity, but not PKCbeta in MKN45 cells, implicating an involvement of PKCalpha in anoikis. Furthermore, vaccinia virus-mediated overexpression of PKCalpha strongly increased CPP32 activity in the detached MKN45 and MKN74 cells, and augmented anoikis, however it had little effect on viability and CPP32 activity in the attached cells. Taken together, PKCalpha promotes apoptotic cell death in gastric cancer cells depending upon loss of anchorage, thereby may be a modulator of anoikis.
Okuda
H
H
The First Department of Internal Medicine, Sapporo Medical University School of Medicine, S1 W16, Chuo-Ku, Sapporo 060-8543, Japan.
Adachi
M
M
Miyazawa
M
M
Hinoda
Y
Y
Imai
K
K
D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009363:Neoplasm Proteins / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D051571:Protein Kinase C-alpha; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects
D007527:Isoenzymes; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D013755:Tetradecanoylphorbol Acetate