Differential functions of PKC-delta and PKC-zeta in cisplatin response of normal and transformed thyroid cells.
We investigated the effects of cisplatin (cisPt) in normal PC Cl3 and in transformed and tumourigenic PC E1Araf cells. cisPt cytotoxicity was higher in PC Cl3 than in PC E1Araf cells. In both cell lines, cisPt provoked the ERK1/2 phosphorylation; this was unaltered by Gö6976, a conventional PKC inhibitor, whilst it was blocked by low doses (0.1 microM) or high doses (10 microM) of GF109203X, an inhibitor of all PKC isozymes, in PC Cl3 and in PC E1Araf cells, respectively. In PC E1Araf, the cisPt-provoked ERK phosphorylation was also blocked by the use of a myristoylated PKC-zeta pseudosubstrate peptide. Conversely, in PC Cl3 the cisPt-provoked ERK phosphorylation was blocked by the use of rottlerin, a PKC-delta inhibitor. Results show that cisPt activates both PKC (the -delta and the -zeta isozymes in PC Cl3 and in PC E1Araf cells, respectively) and ERK in association with prolonged survival of thyroid cell lines.
Urso
L
L
Cell Physiology Laboratory, Dipartimento di Scienze e Tecnologie Biologiche e Ambientali (Di.S.Te.B.A.), Università di Lecce, Italy.
Muscella
A
A
Calabriso
N
N
Ciccarese
A
A
Fanizzi
F P
FP
Migoni
D
D
Di Jeso
B
B
Storelli
C
C
Marsigliante
S
S
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002461:Cell Line, Transformed; D002945:Cisplatin / Q000494:pharmacology* / Q000633:toxicity; D004351:Drug Resistance; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism* / Q000502:physiology; D051745:Protein Kinase C-delta; D051381:Rats; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D000099221:Protein Kinase C zeta
D000970:Antineoplastic Agents; D002945:Cisplatin; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D000099221:Protein Kinase C zeta; C497260:Prkcd protein, rat