UROKINASE-RECEPTOR BIOSYNTHESIS, MESSENGER-RNA LEVEL AND GENE-TRANSCRIPTION ARE INCREASED BY TRANSFORMING GROWTH FACTOR-BETA-1 IN HUMAN A549 LUNG-CARCINOMA CELLS
UROKINASE-RECEPTOR BIOSYNTHESIS, MESSENGER-RNA LEVEL AND GENE-TRANSCRIPTION ARE INCREASED BY TRANSFORMING GROWTH FACTOR-BETA-1 IN HUMAN A549 LUNG-CARCINOMA CELLS
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DOI：
10.1002/j.1460-2075.1991.tb04904.x
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发表时间：
1991-11-01
期刊：
影响因子：
11.4
通讯作者：
DANO, K
中科院分区：
文献类型：
--
作者：
LUND, LR;ROMER, J;DANO, K
我们比较了细胞特异性表达和调节尿激酶型纤溶酶原激活物（u-PAR）的受体转化生长因子β 1型（TGF-β-l）在10个人细胞系来自正常和肿瘤组织。u-PAR mRNA的基础表达及其对TGF-β 1的反应在不同的细胞系之间变化很大;然而，10种细胞系中有5种对TGF-β 1的反应是通过增加u-PAR mRNA水平。其中，A549细胞被选择用于详细阐明参与TGF-β 1调节u-PAR mRNA表达的分子机制。TGF-β-1导致u-PARmRNA水平早期增加，处理24小时后最大增强15倍。这是通过与放射性标记的配体的交联研究检测到的u-PAR蛋白质的增加，也导致细胞表面纤溶酶生成的增加。蛋白质合成抑制剂放线菌酮也以时间依赖性方式增加u-PAR mRNA的水平，当放线菌酮和TGF-β 1同时使用时，可以看到累加效应。核运行的实验表明，只有一个温和的（3倍）增加后，暴露的细胞TGF-β-1 3小时的u-PAR基因转录率相比，在mRNA水平增加12倍。TGF-β-1还引起u-PA和派-1抗原的增加，而对t-PA没有可检测的影响。肿瘤促进剂佛波醇肉豆蔻酸酯乙酸酯和表皮生长因子也强烈增加uPAR mRNA水平在A549和RD细胞，而地塞米松增加u-PAR mRNA水平在RD细胞，但在A549细胞没有效果。
We have compared the cell-specific expression and regulation of the receptor for urokinase-type plasminogen activator (u-PAR) by transforming growth factor-beta type 1 (TGF-beta-l) in 10 human cell lines derived from both normal and neoplastic tissues. The basal expression of u-PAR mRNA as well as its response to TGF-beta-1 varied strongly between different cell lines; however, five out of the 10 cell lines responded to TGF-beta-1 by an increase in the u-PAR mRNA level. Among these, A549 cells were selected for a detailed elucidation of the molecular mechanism involved in TGF-beta-1 regulation of u-PAR mRNA expression. TGF-beta-1 caused an early increase in u-PAR mRNA level, with a maximal 15-fold enhancement after 24 h of treatment. This was paralleled by an increase in u-PAR protein as detected by crosslinking studies with radiolabeled ligand, and also resulted in an increase in cell surface plasmin generation. The protein synthesis inhibitor cycloheximide also increased the level of u-PAR mRNA in a time-dependent fashion and when both cycloheximide and TGF-beta-1 were used, an additive effect was seen. Nuclear run-on experiments demonstrated only a moderate (3-fold) increase in the u-PAR gene transcription rate after exposure of the cells to TGF-beta-1 for 3 h compared with a 12-fold increase in the mRNA level. TGF-beta-1 also caused an increase of both u-PA and PAI-1 antigens, while there was no detectable effect on t-PA. The tumor promoter phorbol myristate acetate and epidermal growth factor also strongly increased the uPAR mRNA level in both A549 and RD cells, whereas dexamethasone increased the u-PAR mRNA level in the RD cells but had no effect in the A549 cells.