Comparison of protein kinase C activity and isoform expression in cisplatin‐sensitive and ‐resistant ovarian carcinoma cells

Abstract

Cellular sensitivity to cis-diamminedichloroplatinum(II) (cDDP) can be regulated by protein kinase C (PKC) signal transduction pathway. Activators of PKC were shown to en- hance 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 J. C13*5.25 cells compared with the drug-sensitive 2008 cells. Subceflular distribution studies revealed a reduction in both cytosolic and paniculate 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 PKCα, -ε, and -ζ isoforms. The abundance of PKCα decreased significantly in 2008/C 13*5.25 cells, whereas the amount of PKCe increased moderately in the resistant variant, with no alteration in PKCε content. Therefore, a reduction in PKCa and/or an increase in PKCε expression may be associated with the drug-resistant phenotype.