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

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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.

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