Quax P H, van Leeuwen R T, Verspaget H W, Verheijen J H
Gaubius Institute TNO, Leiden, The Netherlands.
Cancer Res. 1990 Mar 1;50(5):1488-94.
In 22 human tumor cell lines the regulation of production of plasminogen activators urokinase (u-PA) and tissue-type (t-PA) and their inhibitors PAI-1 and PAI-2 was studied. These four components may determine the net plasminogen activator activity, which is often associated with tumor development and metastatic processes. The amount of specific mRNA and protein produced by the cells was measured for all four components. The frequent finding of t-PA (alone or in combination with u-PA) suggests that t-PA can also be a tumor-associated plasminogen activator. In 11 of the 22 cells PAI-1 mRNA and in 6 of the 22 cells PAI-2 mRNA was found, pointing to a possible role of plasminogen activator inhibitors in the tumor-related plasminogen activator activity. This study demonstrates that there are at least two important regulatory steps in the regulation of production of plasminogen activators and their inhibitors: (a) the regulation at the mRNA level, since a high protein amount is always correlated with a high mRNA amount found in the tumor cells; (b) there must be a significant regulatory step at the (post)translational level as can be concluded from differences in mRNA usage.
在22种人类肿瘤细胞系中，研究了纤溶酶原激活剂尿激酶（u-PA）和组织型（t-PA）及其抑制剂PAI-1和PAI-2的产生调控。这四种成分可能决定纤溶酶原激活剂的净活性，而纤溶酶原激活剂的净活性通常与肿瘤发展和转移过程相关。对所有这四种成分，测量了细胞产生的特异性mRNA和蛋白质的量。经常发现t-PA（单独或与u-PA联合）表明t-PA也可能是一种与肿瘤相关的纤溶酶原激活剂。在22个细胞中的11个中发现了PAI-1 mRNA，在22个细胞中的6个中发现了PAI-2 mRNA，这表明纤溶酶原激活剂抑制剂在肿瘤相关的纤溶酶原激活剂活性中可能发挥作用。本研究表明，在纤溶酶原激活剂及其抑制剂的产生调控中至少有两个重要的调控步骤：（a）在mRNA水平的调控，因为在肿瘤细胞中高蛋白量总是与高mRNA量相关；（b）从mRNA使用差异可以推断，在（翻译后）水平必定存在一个重要的调控步骤。
