Differential functions of PKC-δ and PKC-ζ in cisplatin response of normal and transformed thyroid cells

• Published in: Biochemical and biophysical research communications 2005-11, Vol.337 (1), p.297-305
• Main Authors: Urso, L., Muscella, A., Calabriso, N., Ciccarese, A., Fanizzi, F.P., Migoni, D., Di Jeso, B., Storelli, C., Marsigliante, S.
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - toxicity; Cell Line; Cell Line, Transformed; Cisplatin; Cisplatin - pharmacology; Cisplatin - toxicity; Drug Resistance; ERK; Extracellular Signal-Regulated MAP Kinases - metabolism; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; PC Cl3; Phosphorylation; PKC-δ; PKC-ζ; Protein Kinase C - metabolism; Protein Kinase C - physiology; Protein Kinase C-delta; Rats; Thyroid Gland - cytology; Thyroid Gland - drug effects; Thyroid Gland - enzymology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2005.09.046

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 μM) or high doses (10 μM) 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-ζ pseudosubstrate peptide. Conversely, in PC Cl3 the cisPt-provoked ERK phosphorylation was blocked by the use of rottlerin, a PKC-δ inhibitor. Results show that cisPt activates both PKC (the -δ and the -ζ isozymes in PC Cl3 and in PC E1Araf cells, respectively) and ERK in association with prolonged survival of thyroid cell lines.