| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1994: ¥600,000 (Direct Cost: ¥600,000)
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| Research Abstract |
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
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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
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