TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL REGULATION OF THE RECEPTOR FOR UROKINASE-TYPE PLASMINOGEN-ACTIVATOR BY CYTOKINES AND TUMOR PROMOTERS IN THE HUMAN LUNG-CARCINOMA CELL-LINE A549
TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL REGULATION OF THE RECEPTOR FOR UROKINASE-TYPE PLASMINOGEN-ACTIVATOR BY CYTOKINES AND TUMOR PROMOTERS IN THE HUMAN LUNG-CARCINOMA CELL-LINE A549
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DOI：
10.1042/bj3100345
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发表时间：
1995-08-15
影响因子：
4.1
通讯作者：
DANO, K
中科院分区：
文献类型：
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作者：
LUND, LR;ELLIS, V;DANO, K
尿激酶型纤溶酶原激活剂 (uPAR) 受体是一种整合膜蛋白，可特异性结合尿激酶型纤溶酶原激活剂 (uPA)，在细胞表面纤溶酶生成中发挥至关重要的作用。我们之前发现转化生长因子-β，1 型（TGF-β 1）会增加人肺癌细胞系 A549 中的 uPAR 基因转录，现在报道表皮生长因子（EGF）和肿瘤启动子佛波醇 12-肉豆蔻酸酯 13-乙酸酯（PMA）也会导致 uPAR 转录增加，并且 PMA 和 TGF-β 1 另外会增加 uPAR mRNA 的稳定性，而 EGF 对此参数没有影响。通过放射性标记配体的细胞结合实验测得，所有三种化合物还增加了 uPAR 蛋白水平。然而，所有三种化合物的 uPAR 蛋白水平的增加均远低于 mRNA 水平的增加，表明它们还发挥翻译或翻译后控制作用。随着uPAR分子数量的增加，它们的配体结合亲和力也成比例下降，其机制尚不清楚。血小板源性生长因子、碱性成纤维细胞生长因子和环AMP类似物不会引起A549细胞中uPAR mRNA水平的任何变化。先前的研究表明uPA及其1型抑制剂的表达受到多种细胞因子以细胞特异性的方式调节。本研究表明细胞因子还通过调节 uPAR 表达来影响细胞表面纤溶酶原激活。
The receptor for urokinase-type plasminogen activator (uPAR) is an integral membrane protein that specifically binds urokinase-type plasminogen activator (uPA) and plays a crucial role in cell surface plasmin generation. We have previously found that transforming growth factor-beta, type 1 (TGF-beta 1), increases uPAR gene transcription in the human lung carcinoma cell line A549 and now report that also epidermal growth factor (EGF) and the tumour promoter phorbol 12-myristate 13-acetate (PMA) cause increased uPAR transcription and that PMA and TGF-beta 1 in addition increase the stability of uPAR mRNA, while EGF has no effect on this parameter. All three compounds also increase the uPAR protein level, as measured by cell-binding experiments with radiolabelled ligand. The increase in uPAR protein level was however considerably lower with all three compounds than the increase in mRNA level, suggesting that they also exert a translational or post-translational control. Accompanying the increase in the number of uPAR molecules there was a proportional decrease in their ligand-binding affinity, the mechanism of which is unknown. Platelet-derived growth factor, basic fibroblast growth factor and cyclic AMP analogues did not induce any change in the uPAR mRNA level in A549 cells. Previous studies have shown that expression of uPA and its type-1 inhibitor is regulated by a variety of cytokines in a cell-specific manner. The present study indicates that cytokines in addition influence cell surface plasminogen activation by regulating uPAR expression.