Inhibition of TPA-induced monocytic differentiation in THP-1 human monocytic leukemic cells by staurosporine, a potent protein kinase C inhibitor.
THP-1 is a factor-indepencent, monocytic leukemia cell line which differentiates into adherent macrophages upon treatment with 12-O-tetra-decanoylphorbol-13-acetate (TPA). Unlike its normal counterparts, THP-1 cells display only minimal levels of proto-oncogene c-FMS RNA which encode for membrane M-CSF receptors. Northern blot analysis showed that the c-FMS mRNA levels in THP-1 cells was greatly enhanced during TPA-induced monocytic differentiation. Despite the acquisition of functional activities and induction of c-FMS transcripts after TPA treatment, no surface M-CSF receptors were detected on the THP-1 cells. The inducing activity associated with TPA was completely abrogated when THP-1 cells were pretreated with staurosporine, a potent protein kinase C (PK-C) inhibitor. It is concluded that the activation of the PK-C system is a part of the metabolic cascade essential for the initiation of monocytic differentiation in THP-1 cells.
Barendsen
N
N
Department of Internal Medicine, Wayne State University, Detroit, MI 48201.
Mueller
M
M
Chen
B
B
D000470:Alkaloids / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000473:pathology / Q000502:physiology; D009000:Monocytes / Q000187:drug effects* / Q000473:pathology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D000470:Alkaloids; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016186:Receptor, Macrophage Colony-Stimulating Factor; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate