Expression of the Platelet-derived Growth Factor 1 and 2 Genes in Human Myeloid Cell Lines and Monocytes1

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 r-.v/.vprotooncogene, 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 ex pressed during 12-O-tetradecanoylphorbol-13-acetate (TPA) induced mourn-)ik-differentiation of human 111-60 leukemia cells. In the present study, PDGF-1 and PDGF-2 gene expression was compared in III -60 cells, human THP-1 monocytic leukemia cells, and human monocytes. Uninduced III.-60 cells, uninduced THP-1 cells, and resting monocytes had no detectable PDGF-1 or PDGF-2 mRNA. In contrast, both PDGF1 and PDGF-2 transcripts were detected in III -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 111-60 cells. Cycloheximide, an inhibitor of protein synthesis: (a) failed to increase PDGF-1 and PDGF-2 mRNA levels in uninduced HI -60 cells; (A) increased PDGF2, but not PDGF-1, mRNA in resting monocytes; and (c) increased levels of PDGF-1 and PDGF-2 mRNA in III -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 mecha nisms 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.