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Analyzes of the role of urokinase receptor cell growth

尿激酶受体细胞生长作用的分析

基本信息

批准号：
06670052
负责人：
URANO Tetsumei
金额：
$ 1.28万
依托单位：
HAMAMATSU UNIVERSITY SCHOOL OF MEDICINE
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

项目摘要

(1) We studied the expression of uPAR mPNA in cultured cell line (U-937). The expression of uPAR mRNA was enhanced by phorbol-ester stimulation, which resulted in the higher accumulation of uPAR antigen both in the medium and in the cell lysate. We detected two different forms of uPAR mRNA,one of which coodes mature uPAR and another codes soluble uPAR.Employing two different DNA probes, each of which detects only one of these two different mRNAs, we demonstrated that both forms increased after phorbol ester stimulation.(2) We assayd antigen levels of soluble uPAR in cancer patients plasma. In lung cancer patients, plasma soluble uPAR levels were significantly higher than those in normal controls. Either by proteolytic cleavage of mature uPAR or by increasing alternatively spliced mRNA for soluble uPAR,plasma uPAR seems to be elevated. Plasma soluble uPAR level might be a useful tumor marker of lung cancer.(3) The expression of uPA mRNA in lung cancer tissue was significantly higher than that in normal lung tissue. The expression of uPAR mRNA,however, did not differ between cancer tissue and normal lung tissue. mRNA of both PAI-1 and PAI-2 were also higher in lung cancer tissue than those in normal counter parts, which are in accordance with our previous results of their antigen level.(4) We analyzed the effects of either uPA alone or of uPA together with its specific inhibitor on cell growth using U937. uPA alone slightly enhanced cell growth. Simultancous use of its inhibitor, however, did not influence cell growth. Since U937 without treatment by phorbol-ester may not have enough amounts of uPAR on cell surface, further experiment using other cell line must be needed to clarify the effect of uPA and its inhibitors on cell growth.

(1)我们研究了uPAR mPNA在培养细胞系U-937中的表达。佛波醇酯刺激可增强uPAR mRNA的表达，从而导致uPAR抗原在培养基和细胞裂解液中的积累。我们检测到两种不同形式的uPAR mRNA，其中一种编码成熟uPAR，另一种编码可溶性uPAR。使用两种不同的DNA探针，每种探针只能检测这两种不同mRNA中的一种，我们证明了两种形式在佛波醇酯刺激后都增加。(2)我们测定了癌症患者血浆中可溶性uPAR的抗原水平。肺癌患者血浆可溶性uPAR水平显著高于正常对照组。通过成熟uPAR的蛋白水解裂解或通过增加可溶性uPAR的选择性剪接mRNA，血浆uPAR似乎升高。血浆可溶性uPAR水平可能是肺癌的一个有用的肿瘤标志物。(3)肺癌组织中uPA mRNA的表达明显高于正常肺组织。而uPAR mRNA的表达在癌组织和正常肺组织中无明显差异。派-1和派-2的mRNA在肺癌组织中的表达也高于正常对照组织，这与我们以前的研究结果相一致。(4)我们使用U937分析了单独的uPA或uPA与其特异性抑制剂一起对细胞生长的影响。单独的uPA略微增强细胞生长。然而，同时使用其抑制剂并不影响细胞生长。由于未经佛波酯处理的U937细胞表面可能没有足够量的uPAR，因此必须使用其他细胞系进行进一步的实验以阐明uPA及其抑制剂对细胞生长的影响。