Since PKC epsilon functions as an oncogene when stably overexpressed in R6 rat fibroblasts (Cacace et al. 1993) in the present study we examined whether transformed R6-PKC epsilon cells display abnormalities in the expression of specific early response and cyclin genes. When vector control and R6-PKC epsilon 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 PKC epsilon cells, induction of cyclin D1 protein was markedly reduced, and that of cyclin A was slightly reduced when compared to control cells. Northern blot analyses indicated that decreased expression of cyclin D1 and A protein in PKC epsilon cells is due to translational or post-translational effects. A study of early response gene expression in PKC epsilon 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 cyclin D1 and c-fos expression seen in PKC epsilon cells were not seen in R6 cells that overexpress PKCs alpha or beta. These findings suggest that PKC epsilon cells bypass certain normal signal transduction and cyclin-controlled pathways involved in cell proliferation.