ALTERED EXPRESSION OF CYCLINS AND C-FOS IN R6 CELLS THAT OVERPRODUCE PKC-EPSILON

Since PKC epsilon functions as an oncogene when stably overexpressed i n R6 rat fibroblasts (Cacace et al. 1993) in the present study we exam ined whether transformed R6-PKC epsilon cells display abnormalities in the expression of specific early response and cyclin genes. When vect or control and R6-PKC epsilon cells were starved of serum for 72 h the y arrested in G0/G1 and showed passage through the cell cycle at simil ar rates after subsequent stimulation with 10% fetal calf serum plus T PA. In PKC epsilon cells, induction of cyclin D1 protein was markedly reduced, and that of cyclin A was slightly reduced when compared to co ntrol cells. Northern blot analyses indicated that decreased expressio n of cyclin D1 and A protein in PKC epsilon cells is due to translatio nal or post-translational effects. A study of early response gene expr ession in PKC epsilon cells indicated that there was a marked reductio n 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 epsilo n cells were not seen in R6 cells that overexpress PKCs alpha or beta. These findings suggest that PKC epsilon cells bypass certain normal s ignal transduction and cyclin-controlled pathways involved in cell pro liferation.