Mäkelä T P, Alitalo R, Paulsson Y, Westermark B, Heldin C H, Alitalo K
Department of Virology, University of Helsinki, Finland.
Mol Cell Biol. 1987 Oct;7(10):3656-62. doi: 10.1128/mcb.7.10.3656-3662.1987.
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.
我们研究了血小板衍生生长因子（PDGF）A链和B链编码基因在多种人类白血病细胞系中的表达情况。仅在单核细胞白血病细胞系U937和T细胞白血病细胞系MOLT-4中观察到A链RNA的稳态表达。此前有报道称，PDGF A和PDGF B基因在K562红白血病细胞的巨核细胞分化过程中被诱导，并且在早幼粒细胞白血病细胞系HL-60和U937细胞的单核细胞分化过程中短暂诱导。在本研究中，我们发现用8 pM浓度的转化生长因子β（TGF-β）刺激1至2小时后，HL-60和Jurkat T细胞白血病细胞中诱导了PDGF A RNA表达，U937和MOLT-4细胞中其表达增加。在U937细胞中，PDGF A RNA至少24小时保持在恒定的升高水平，但在HL-60细胞中12小时内恢复到不可检测水平。TGF-β在K562细胞或肺癌细胞（A549）中未诱导PDGF A表达。有趣的是，基本上没有PDGF B链（c-sis原癌基因）RNA与PDGF A同时表达。在TGF-β和蛋白质合成抑制剂存在的情况下，U937和HL-60细胞中PDGF A RNA被超诱导至少20倍。PDGF A的表达伴随着可免疫沉淀的PDGF分泌到HL-60和U937细胞的培养基中。佛波酯肿瘤启动子十四酰佛波醇乙酸酯也以类似的动力学增加PDGF A表达，但机制与TGF-β不同。这些结果表明TGF-β在PDGF基因表达的差异调节中起作用。
