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

尿激酶型纤溶酶原激活剂和纤溶酶原激活剂抑制剂2的基因表达

基本信息

批准号：
06671079
负责人：
NIIYA Kenji
金额：
$ 1.22万
依托单位：
Toyama Medical and Pharmaceutical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671079/
关键词：
Urokinase PAI-2 Protein kinase C cAMP-dependent protein kinase Cytokines PGI2 Gene expresion Leukemia lymphoma cells urokinase gene expression cytokines cAMP LPS TRE AP1 c-fos NFkB

项目摘要

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

研究了肉豆蔻酸佛波酯（PMA）（一种蛋白激酶C、cAMP和细胞因子的激活剂）对RC-K8淋巴瘤和PL-21白血病细胞系中的尿激酶型纤溶酶原激活物（uPA）和纤溶酶原激活物抑制剂-2（派-2）的影响。结果表明，cANP通过抑制uPA基因转录而减少RC-K8细胞中uPA的产生，其中不需要从头蛋白合成，并且其依赖于蛋白激酶活性（BBA 1268，1995）。用前列腺素12的稳定类似物贝前列素处理RC-K8细胞，导致uPA mRNA减少（Thromb Haemost，1996，出版中）。IL-1 I型受体存在于RC-K8细胞表面，IL-1 α和IL-1 β均诱导细胞中uPA基因转录（Thromb Haemost 74，1995）。使用双链AP 1 oligo的电迁移率变动分析揭示了RC-K8细胞中存在TPA-反应元件结合蛋白（TREB），并且用PMA刺激可以增加TREB，但不能增加TREB。 ...更多信息 t与IL-1的表达，表明TREB可能参与RMA诱导的uPA表达。cAMP和PMA都能诱导PL-21细胞中的派-2，但cAMP和PMA刺激后的信号转导途径战神不同的，尽管两种途径之间必然存在串扰（Thromb Haemost 72，1994）。PL-21细胞中存在一对TREB，用RT-PCR方法证实反义S oligo对PMA诱导的派-2基因表达有抑制作用。脂多糖（LPS）可诱导RC-K8和PL-21细胞中uPA和派-2的表达。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CD 14不存在于PL-21细胞表面，因此LPS可能通过未知的途径诱导uPA。为了研究这些uPA和派-2基因在恶性细胞中的表达，目前还没有完全了解，与瑞士Friedrich Miescher研究所的合作研究将于今年开始。少