Increased expression of ornithine decarboxylase by gamma-ray in mouse epidermal cells: relationship with protein kinase C signaling pathway.

The correlation between ornithine decarboxylase (ODC) protein induction and specific protein kinase C (PKC) isozyme expression by gamma-ray in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated normal and v-rasHa transformed mouse keratinocytes was examined. TPA at 100 nM was treated in primary mouse keratinocytes immediately after 4 Gy, 8 Gy and 16 Gy gamma-ray irradiation. After 4 hrs, cells were harvested and the protein expression levels of PKC isozymes (PKC alpha, -delta, -epsilon, -eta and -zeta) and ODC were examined. For v-rasHa infection, primary keratinocytes were infected with a defected retrovirus containing the v-rasHa gene. After 3 hrs of irradiation, each PKC isozyme and ODC protein expression were tested. Gamma-ray increases ODC protein expression in both TPA-treated normal and v-rasHa transformed mouse keratinocytes and this phenomenon correlated to the increased induction of PKC alpha without altering other PKC isozymes. Tyrosine phosphorylation of epidermal growth factor receptor protein was also stimulated during gamma-ray induced cellular changes in TPA-treated normal mouse keratinocytes. These results indicate that PKC alpha as an important regulator of mouse epidermal changes by gamma-radiation, contributes to the ODC expression occurring during exposure to tumor promoter, such as TPA, and epidermal neoplasia induced by ras activation.