Protein Kinase C fi Gene Expression Is Associated with Susceptibility of Human Promyelocytic Leukemia

To study the signal transduction pathway leading to phorbol 1 2-myristate 13-acetate (PMA)-induced differentiation in human promyelocytic HL-60 leukemia cells, we examined the expression of protein kinase C (PKC) isozyme genes in HL-60 cells that are susceptible or resistant to PMA-induced differentiation. The PKC-a,-fi,-7,-o,#{128},and transcript levels were assessed by Northern blotting, and the PKC-a,-ft, and-y protein levels were examined by immunoblotting. The PMA-resistant cell variants HL-525 and HL-534 were found to be deficient in the PKC- isozyme RNA and protein as compared with the PMA-susceptible HL-60 and HL-205 cell lines. In addition, a “8-like ” PKC RNA species identified in these cells demonstrated a reduced abundance in the HL-525 and HL-534 cells. Southern blot analysis indicated that the observed reduction in PKC-ft gene expression does not appear to be due to a gross deletion or rearrangement of the gene. The expression of the early response genes junB, c-los, and c-jun was attenuated in PMA-treated HL-525 and HL-534 cells as compared to the PMA-treated HL-60 and HL-205 cells. These results suggest that the signal transduction pathway that leads to PMA-induced differentiation in the HL-60 cell system requires PKC- and/or 6-like PKC for the proper expression of the early response genes, and ultimately the expression of genes that define the mature state