Abstract
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.
This investigation was supported by USPHS Grants CA34183 and CA42802 awarded by the National Cancer Institute, Department of Health and Human Services, by a Burroughs Wellcome Clinical Pharmacology Scholar Award [D. K.], and by a NATO grant [E. S.].