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The role of Fas/Fas ligand system in human

Fas/Fas配体系统在人体中的作用

基本信息

批准号：
08671571
负责人：
TACHIBANA Osamu
金额：
$ 1.41万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671571/
关键词：
Fas ligand apoptosis glioblastoma ICE ICH-1 CPP32 神経膠芽腫 Fas アポトーシス

项目摘要

Fas/APO-1 (CD95) is a cell surface receptor that mediates apoptosis when it reacts with Fas ligand (FasL) or Fas antibody. I previously reported that Fas expression in predominantly induced in perinecrotic glioma cells, suggesting that Fas induction is associated with apoptosis and necrosis formation, a histological hallmark of glioblastomas. Cysteine proteases of caspase family {interleukin-1 beta-converting enzyme (ICE)} have been implicated as components of cell death pathway and have been reported to involved in Fas, chemotherapeutic agents, and radiation-induced apoptosis. In this study, I assessed the expression lf FasL,ICE,ICE/CED-3 homologue-IL (ICH-1), and CPP32/Yama/apopain in 13 cases of primary astrocytic brain tumors (two low grade astrocytomas, five anaplastic astrocytomas, and six glioblastomas) by reverse transcription (RT) -PCR,Western blot analysis, and immunohistochemistry. RT-PCR revealed that all astrocytic brain tumors express FasL.Immunohistochemically, FasL was predominantly expressed on the plasma membrane of glioma cells. These results suggest that FasL expression is common in human astrocytic brain tumors and may cause apoptosis of glioma cells if Fas expression is induced. The frequency of ICE,ICH-1, and CPP32 overexpression appears to correlate with the malignacy grade of astrocytic brain tumors. Furthermore, ICH-1 and CPP32 overexpression may play an important role in the pathogenesis of necrosis, which is one of the histological hallmarks of glioblastoma.

Fas/APO-1(CD95)是一种细胞表面受体，当它与Fas配体(FasL)或Fas抗体反应时，介导细胞凋亡。我以前曾报道Fas的表达主要诱导在坏死周围的胶质瘤细胞中，提示Fas诱导与细胞凋亡和坏死形成有关，这是胶质母细胞瘤的组织学标志。半胱氨酸蛋白酶家族的半胱氨酸蛋白酶(IL-1β-转换酶，ICE)被认为是细胞死亡途径的组成部分，并已被报道参与Fas、化疗药物和辐射诱导的细胞凋亡。本研究采用逆转录-聚合酶链式反应(RT-PCR)、免疫印迹分析和免疫组织化学方法，检测了13例原发星形细胞脑瘤(2例低度恶性星形细胞瘤、5例间变性星形细胞瘤和6例胶质母细胞瘤)中FasL、ICE、ICE/CED-3同源IL(ICH-1)和CPP32/YAMA/AAPPAIN的表达。RT-PCR显示，所有星形细胞脑瘤均表达FasL。免疫组织化学显示，FasL主要表达于胶质瘤细胞的质膜上。这些结果表明，FasL在人脑星形细胞肿瘤中的表达是常见的，如果Fas表达被诱导，可能会导致胶质瘤细胞的凋亡。ICE、ICH-1和CPP32过表达的频率似乎与星形细胞脑瘤的恶性程度有关。此外，ICH-1和CPP32的过度表达可能在肿瘤坏死的发病机制中起重要作用，而坏死是胶质母细胞瘤的组织学标志之一。