Protein kinase C beta gene expression is associated with susceptibility of human promyelocytic leukemia cells to phorbol ester-induced differentiation.
To study the signal transduction pathway leading to phorbol 12-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-alpha, -beta, -gamma, -delta, epsilon, and -zeta transcript levels were assessed by Northern blotting, and the PKC-alpha, -beta, and -gamma protein levels were examined by immunoblotting. The PMA-resistant cell variants HL-525 and HL-534 were found to be deficient in the PKC-beta isozyme RNA and protein as compared with the PMA-susceptible HL-60 and HL-205 cell lines. In addition, a "delta-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-beta 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-fos, 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-beta and/or delta-like PKC for the proper expression of the early response genes, and ultimately the expression of genes that define the mature state.
Tonetti
D A
DA
Biological and Medical Research Division, Argonne National Laboratory, Illinois 60439.
Horio
M
M
Collart
F R
FR
Huberman
E
E
D002454:Cell Differentiation / Q000187:drug effects; D004351:Drug Resistance; D004790:Enzyme Induction / Q000187:drug effects; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology*; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011493:Protein Kinase C / Q000235:genetics / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D009363:Neoplasm Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate