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 C13 than in PC ElAraf cells. In both cell lines, cisPt provoked the ERK1/2 phosphorylation; this was unaltered by Go6976, a conventional PKC inhibitor, whilst it was blocked by low doses (0. 1 mu M) or high doses (10 mu M) of GF109203X, an inhibitor of all PKC isozymes, in PC C13 and in PC ElAraf cells, respectively. In PC ElAraf, the cisPt-provoked ERK phosphorylation was also blocked by the use of a myristoylated PKC-xi pseudosubstrate peptide. Conversely, in PC C13 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 -xi isozymes in PC C13 and in PC ElAraf cells, respectively) and ERK in association with prolonged survival of thyroid cell lines. (c) 2005 Elsevier Inc. All rights reserved.