Necrogenesis in human astrocytic tumors especially based on decoy receptor 3 gene amplification and expression

人类星形细胞肿瘤的坏死，特别是基于诱饵受体 3 基因扩增和表达

• 批准号: 12671346
• 负责人: TACHIBANA Osamu
• 金额: $ 2.24万
• 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: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671346/
• 关键词: decoy receptor 3; glioblastoma; Fas; Fas-ligand; glioblastoma

Decoy receptor 3 (DcR3), a secreted member of the tumor necrosis factor receptor superfamily, is amplified at high frequency in human lung and colon. In this study, I examined the DcR3 gene amplification by semi-quantitative genomic PCR in 57 human astrocytic brain tumors, including 34 glioblastomas and DcR3 mRNA expression by real-time semi-quantitative reverse transcription-PCR in 24 astrocytic brain tumors, including 13 glioblastomas. DcR3 gene amplification was detected in none of 7 (0%) low-grade astrocytomas, 1 of 17 (5.9%) anaplastic astrocytomas, and 7 of 34 (20.6%) glioblastomas. DcR3 mRNA tend to express high in glioblastomas than low grade astrocytomas. A well correlation between DcR3 gene amplification and mRNA expression was found in 24 astrocytic tumors. Expression of DcR3 mRNA in human astrocytic tumors was dependent of gene amplification. Immunoreactivity to Fas was observed in a large number of glioblastoma cases. These results suggest that high DcR3 expression with gene amplification might be responsible to malignant featuresin high grade astrocytic tumors, that may be attributed to escape from FasL-Fas mediated cell death.

诱骗受体3（DcR 3）是肿瘤坏死因子受体超家族的分泌型成员，在人肺和结肠中以高频率扩增。在这项研究中，我通过半定量基因组PCR检测了57例人类星形细胞脑肿瘤（包括34例胶质母细胞瘤）中的DcR 3基因扩增，并通过实时半定量逆转录PCR检测了24例星形细胞脑肿瘤（包括13例胶质母细胞瘤）中的DcR 3 mRNA表达。7例低级别星形细胞瘤中无一例（0%）DcR 3基因扩增，17例间变性星形细胞瘤中1例（5.9%），34例胶质母细胞瘤中7例（20.6%）。DcR 3 mRNA在胶质母细胞瘤中的表达高于低级别星形细胞瘤。24例星形细胞肿瘤中DcR 3基因扩增与mRNA表达呈显著正相关。DcR 3 mRNA在人脑星形细胞肿瘤中的表达依赖于基因扩增。在大量胶质母细胞瘤病例中观察到对Fas的免疫反应性。这些结果表明，DcR 3高表达和基因扩增可能是导致高级别星形细胞肿瘤恶性特征的原因，这可能归因于逃避FasL-Fas介导的细胞死亡。