A protective role of PKCepsilon against TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in glioma cells.
To elucidate the molecular mechanism(s) involved in the TRAIL-induced apoptosis sensitivity, we conducted the following experiments utilizing TRAIL-sensitive and -resistant glioma cells. We examined the expression of TRAIL receptors mRNA, but no significant differences were detected in those cells. TRAIL-resistant cells were sensitized to TRAIL-induced apoptosis by staurosporine pretreatment and preferentially expressed PKCepsilon. Since several lines of evidence suggest that PKC may play a protective role for apoptosis, we analyzed the involvement of PKCepsilon in TRAIL-induced apoptosis by an adenovirus vector expression system. We found that TRAIL susceptibility was augmented by the expression of a dominant negative PKCepsilon in TRAIL-resistant cells. Conversely, PKCepsilon introduction in TRAIL-sensitive cells resulted in the reduction of TRAIL-induced apoptosis. Taken together, these data suggest that PKCepsilon may be a regulator of susceptibility to TRAIL-induced apoptosis in gliomas and probably other malignancies.
Shinohara
H
H
Department of Retroviral Regulation, Medical Research Division, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113-8519, Japan.
Kayagaki
N
N
Yagita
H
H
Oyaizu
N
N
Ohba
M
M
Kuroki
T
T
Ikawa
Y
Y
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002470:Cell Survival / Q000187:drug effects; D004347:Drug Interactions; D005910:Glioma; D006801:Humans; D007527:Isoenzymes / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D011493:Protein Kinase C / Q000494:pharmacology*; D051744:Protein Kinase C-epsilon; D053221:TNF-Related Apoptosis-Inducing Ligand; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D051017:Apoptosis Regulatory Proteins; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D020011:Protective Agents; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; C497255:PRKCE protein, human; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon