Regulation of platelet-derived growth factor gene expression by transforming growth factor beta and phorbol ester in human leukemia cell lines.
We studied the expression of the genes encoding the A and B chains of platelet-derived growth factor (PDGF) in a number of human leukemia cell lines. Steady-state expression of the A-chain RNA was seen only in the promonocytic leukemia cell line U937 and in the T-cell leukemia cell line MOLT-4. It has previously been reported that both PDGF A and PDGF B genes are induced during megakaryoblastic differentiation of the K562 erythroleukemia cells and transiently during monocytic differentiation of the promyelocytic leukemia cell line HL-60 and U937 cells. In this study we show that PDGF A RNA expression was induced in HL-60 and Jurkat T-cell leukemia cells and increased in U937 and MOLT-4 cells after a 1- to 2-h stimulation with an 8 pM concentration of transforming growth factor beta (TGF-beta). PDGF A RNA remained at a constant, elevated level for at least 24 h in U937 cells, but returned to undetectable levels within 12 h in HL-60 cells. No PDGF A expression was induced by TGF-beta in K562 cells or in lung carcinoma cells (A549). Interestingly, essentially no PDGF B-chain (c-sis proto-oncogene) RNA was expressed simultaneously with PDGF A. In the presence of TGF-beta and protein synthesis inhibitors, PDGF A RNA was superinduced at least 20-fold in the U937 and HL-60 cells. PDGF A expression was accompanied by secretion of immunoprecipitable PDGF to the culture medium of HL-60 and U937 cells. The phorbol ester tumor promoter tetradecanoyl phorbol acetate also increased PDGF A expression with similar kinetics, but with a mechanism distinct from that of TGF-beta. These results suggest a role for TGF-beta in the differential regulation of expression of the PDGF genes.
D002454:Cell Differentiation; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D046911:Macromolecular Substances; D010455:Peptides / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000235:genetics* / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000235:genetics; D013997:Time Factors; D015291:Transforming Growth Factors; D014407:Tumor Cells, Cultured / Q000502:physiology*
C000715470:MAS1 protein, human; D046911:Macromolecular Substances; D010455:Peptides; D010703:Phorbol Esters; D010982:Platelet-Derived Growth Factor; D011500:Protein Synthesis Inhibitors; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D015291:Transforming Growth Factors