Gene Expressions of Urokinase-type Plasminogen Activator and Plasminogen Activator Inhibitor-2

我研究了肉豆蔻酸酯（PMA），一种蛋白激酶C的激活剂，cAMP和细胞因子对RC-K8淋巴瘤和PL-21白血病细胞系尿激酶型纤溶酶原激活剂（uPA）和纤溶酶原激活剂抑制剂-2 （PAI-2）的影响。结果表明，cANP通过抑制uPA基因转录减少RC-K8细胞中uPA的产生，在此过程中，新的蛋白质合成是不必要的，它依赖于蛋白激酶活性（BBA 1268,1995）。用Beraprost（一种稳定的前列腺素12类似物）处理RC-K8细胞，导致uPA mRNA的减少（Thromb Haemost, 1996, in press）。IL-1型受体存在于RC-K8细胞表面，IL-1 α和β均可诱导细胞内uPA基因的转录（Thromb Haemost 74,1995）。利用双链AP1寡核苷酸的电迁移性转移实验显示，在RC-K8细胞中存在tpa反应元件结合蛋白（TREB），且TREB在PMA刺激下升高，但在IL-1刺激下没有升高，提示TREB可能参与rma诱导的uPA表达。cAMP和PMA都能在PL-21细胞中诱导PAI-2，但cAMP和PMA刺激后的信号转导途径不同，尽管两种途径之间一定存在串扰（Thromb Haemost 72,1994）。在PL-21细胞中存在一对TREB，并通过RT-PCR方法证实了反义S oligo对c-fos cDNA的抑制作用对pma诱导的pai -2基因的表达。脂多糖（LPS）在RC-K8和PL-21细胞中分别诱导了uPA和PAI-2。LPS诱导uPA独立于IL-1途径（Thromb Haemost 74,1995）。有趣的是，被认为是LPS受体的CD14并不存在于PL-21细胞表面，因此LPS可能通过未知途径诱导uPA。为了研究这些uPA和PAI-2基因在恶性细胞中的表达，我们将于今年开始与瑞士Friedrich Miescher研究所的合作研究。少

I have investigated the effects of phrobol myristate acetate (PMA), an activator of protein kinase C,cAMP and cytokines on urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-2 (PAI-2) in RC-K8 lymphoma and PL-21 leukemia cell lines. The results show that cANP decreases uPA production in RC-K8 cells through suppressing uPA gene transcription and in which de novo protein synthesis is not necessary, and it is dependent of protein kinase activity (BBA 1268,1995). Treatment of RC-K8 cells with Beraprost, a stable analogue of prostaglandin 12, resulted in a decrease of uPA mRNA (Thromb Haemost, 1996, in press). IL-1 type I receptor is present on the RC-K8 cell-surface, and both IL-1alpha, beta induce uPA gene transcription in the cells (Thromb Haemost 74,1995). Elecromobility shift assay using the double stranded AP1 oligo revealed the presence of TPA-response element binding proteins (TREB) in RC-K8 cells and the TREB was increased by stimulation with PMA, but no … More t with IL-1, suggesting the TREB may be involved in RMA-induced uPA expression. Both cAMP and PMA can induce PAI-2 in PL-21 cells but the signal transduction pathways after cAMP and PMA stimulation ares different, although there must be a crosstalk between two pathways (Thromb Haemost 72,1994). A couple of TREB are present in PL-21 cells and the inhibitory effect of antisense S oligo against c-fos cDNA on PMA-induced PAI-2gene expression was demonstrated by RT-PCR method. Lipopolysaccharide (LPS) induced uPA and PAI-2 in RC-K8 and PL-21 cells, respectively. LPS induces uPA independently of the IL-1 pathway (Thromb Haemost 74,1995). Interestingly, CD14 which is believed to be a LPS-receptor is not present on the PL-21 cell surface, therefore LPS might induce uPA through the unknown pathway. To investigate these uPA and PAI-2 gene expression in malignant cells which are still not fully understood, collaboration study with Friedrich Miescher Institute in Switzerland will start in this year. Less