Altered expression of cyclins and c-fos in R6 cells that overproduce PKCε

Abstract

Since PKCε functions as an oncogene when stably overex pressed in R6 rat fibroblasts (Cacace et al. 1993) in the present study we examined whether transformed R6-PKCa cells display abnormalities in the expression of specific early response and cydlin genes. When vector control and R6-PKCε cells were starved of serum for 72 h they arrested in G0/G1 and showed passage through the cell cycle at similar rates after subsequent stimulation with 10% fetal calf serum plus TPA. In PKCε cells, induction of cyclin Dl protein was markedly reduced, and that of cydin A was slightly reduced when compared to control cells. Northern blot analyses indicated that decreased expression of cydlin D1 and A protein in PKCε cells Is due to translational or post-translational effects. A study of early response gene expression in PKCε cells indicated that there was a marked reduction in the expression of c-fos mRNA but not in c jun or c-myc mRNAs. The marked decreases in cydlin D1 and c-fos expression seen in PKCε cells were not seen in R6 cells that overexpress PKCs α or β. These findings suggest that PKCE cells bypass certain normal signal transduction and cydin-controlled pathways involved in cell proliferation.