Comparison of protein kinase C activity and isoform expression in cisplatin-sensitive and -resistant ovarian...

Cellular sensitivity to cis-diamminedichloroplatinum(II) (cDDP) can be regulated by protein kinase C (PKC) signal transduction pathway. Activators of PKC were shown to enhance the sensitivity of human ovarian carcinoma 2008 cells to cDDP. We have examined whether or not the PKC signal transduction pathway is affected during development of resistance by tumor cells to cDDP. A 2-fold decrease in PKC activity was observed in cDDP-resistant ovarian carcinoma 2008/C13*5.25 cells compared with the drug-sensitive 2008 cells. Subcellular distribution studies revealed a reduction in both cytosolic and particulate PKC activities in 2008/C13*5.25 cells. The pattern of PKC isoform expression was compared in cDDP-sensitive and -resistant cell lines by Western blot analysis with isoform-specific antibodies to PKC. The parental cells expressed PKC alpha, -epsilon, and -zeta isoforms. The abundance of PKC alpha decreased significantly in 2008/C13*5.25 cells, whereas the amount of PKC epsilon increased moderately in the resistant variant, with no alteration in PKC zeta content. Therefore, a reduction in PKC alpha and/or an increase in PKC epsilon expression may be associated with the drug-resistant phenotype.