The role of the c-fms oncogene in the regulation of HL-60 cell differentiation.
Human promyelocytic leukemia HL-60 cells were induced to differentiate into macrophages by PMA (phorbol 12-myristate-13-acetate), 1-alpha-25-(OH)2D3(1-alpha-25-dihydroxyvitamin D3, hrGM-CSF (human recombinant granulocyte-macrophage colony-stimulating factor) and into granulocytes by DMSO (dimethylsulfoxide). We found that the differentiation of HL-60 cells into macrophages was accompanied by transcription of the c-fms oncogene, which was assessed by a modified PCR (polymerase-chain reaction) method. After treatment with a c-fms anti-sense oligomer, the PMA and hrGM-CSF induced macrophage differentiation of HL-60 cells was significantly inhibited, whereas either 1-alpha-25-(OH)2D3 induced macrophage or DMSO and hrGM-CSF induced granulocytic differentiation was not inhibited. Furthermore, we treated the HL-60 cells with M-CSF (macrophage-colony stimulating factor or CSF-1) anti-sense N degrees 2 (see Figure 1) in the presence of PMA, hrGM-CSF, 1-alpha-25-(OH)2D3 and DMSO. The results showed that this treatment leads to a significant inhibition of PMA and hrGM-CSF-induced macrophage differentiation, but has no influence on the 1-alpha-25-(OH)2D3-induced macrophage differentiation and DMSO-induced granulocytic differentiation. It was further demonstrated that the M-CSF (or CSF-1) and c-fms antisense oligomers acted synergistically on inhibition of macrophage formation induced by PMA and hrGM-CSF, but had no inhibitory effect on the macrophage formation induced by 1-alpha-25-(OH)2D3. Thus we concluded firstly, that HL-60 cells differentiate into macrophages along two different pathways: one is involved in the action of the c-fms oncogene and the other is not. Secondly, an autocrine circuit of M-CSF (or CSF-1) action may exist in the macrophage formation induced by PMA and hrGM-CSF.
Wu
J
J
Department of Biochemistry, Nanjing University, People's Republic of China.
Zhu
J Q
JQ
Han
K K
KK
Zhu
D X
DX
D001483:Base Sequence; D002117:Calcitriol / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000473:pathology; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D016173:Macrophage Colony-Stimulating Factor; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D016186:Receptor, Macrophage Colony-Stimulating Factor; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D009841:Oligonucleotides; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate; D004121:Dimethyl Sulfoxide