Inhibition of expression of PKC-alpha by antisense mRNA is associated with diminished cell growth and inhibition of amylase secretion by AR4-2J cells.

AR4-2J pancreatoma cells were stably transfected with an expression vector containing the cDNA for PKC-alpha in the antisense orientation. Transfectants designated antisense-alpha AA1, AA2, and AA3 exhibited marked reductions in PKC-alpha expression and decrements in cell growth. The magnitude of the decrement in cell growth paralleled the reduction in PKC-alpha expression, i.e., AA3 > AA1 > AA2. The ability of dexamethasone to induce cell differentiation as assessed by a rise in cellular amylase levels was not markedly affected by the reduction in PKC-alpha expression. Unstimulated amylase release was attenuated in AA1 cells and almost completely blocked in AA2 transfectants. The AA2 transfectant cell line failed to elicit a secretory response to caerulein, and the AA1 transfectant exhibited a lack of the secondary phase of stimulated amylase secretion. These findings demonstrate that PKC-alpha is involved in the mechanisms regulating growth and secretion in AR4-2J cells, but is not necessary for the induction of amylase stores following differentiation.