Expression of the platelet-derived growth factor 1 and 2 genes in human myeloid cell lines and monocytes.
Platelet-derived growth factor (PDGF), a potent mitogen for mesenchymal cells, consists of PDGF-1 and PDGF-2 polypeptide chains which are linked by disulfide bonds. Sequence analysis has revealed that: (a) the PDGF-2 chain is encoded by the c-sis protooncogene, the cellular counterpart of the simian sarcoma viral oncogene; (b) the PDGF-1 and PDGF-2 chains are related; and (c) the PDGF-1 gene has no known viral homologue. We have previously shown that the PDGF-2 gene is expressed during 12-O-tetradecanoylphorbol-13-acetate (TPA) induced monocytic differentiation of human HL-60 leukemia cells. In the present study, PDGF-1 and PDGF-2 gene expression was compared in HL-60 cells, human THP-1 monocytic leukemia cells, and human monocytes. Uninduced HL-60 cells, uninduced THP-1 cells, and resting monocytes had no detectable PDGF-1 or PDGF-2 mRNA. In contrast, both PDGF-1 and PDGF-2 transcripts were detected in HL-60 cells and monocytes induced with TPA, while only PDGF-1 mRNA was found in TPA-treated THP-1 cells. Moreover, neither of these transcripts were found during drug induced granulocytic differentiation of HL-60 cells. Cycloheximide, an inhibitor of protein synthesis: (a) failed to increase PDGF-1 and PDGF-2 mRNA levels in uninduced HL-60 cells; (b) increased PDGF-2, but not PDGF-1, mRNA in resting monocytes; and (c) increased levels of PDGF-1 and PDGF-2 mRNA in HL-60 cells and monocytes treated with TPA. This effect of cycloheximide was related in part to stabilization of both transcripts. Thus, PDGF-1 and PDGF-2 genes are differentially regulated in myeloid cells, although they share common control mechanisms at the post-transcriptional level. Differential regulation of PDGF gene expression would result in altered chain composition of the PDGF protein and possibly changes in biological activity.
Sariban
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Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Kufe
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D002454:Cell Differentiation; D003513:Cycloheximide / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D013755:Tetradecanoylphorbol Acetate; D014407:Tumor Cells, Cultured
D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate