当一个 Wnt 对手和肿瘤 suppressor,而是 WIF-1 基因倡导者和 WIF-1 的低表示的 hypermethylation 激活异常地发信号的 Wnt 并且导致几个人的肿瘤的开发, Wnt 禁止的 factor-1 (WIF-1 ) 行动。由使用 RT-PCR, immunohistochemistry 和 methylation 特定的 PCR,我们在 4 正常大脑纸巾分析了 WIF-1 的表示和 methylation, 35 刚 resected 星细胞瘤纸巾和 4 根导出 glioblastoma 的房间线。WIF-1 mRNA 和蛋白质表示层次的重要 downregulation 与正常大脑纸巾相比在星细胞瘤纸巾被观察。在 WIF-1 downregulation 和星细胞瘤的病理学的等级之间的重要协会被发现。WIF-1 基因异常 methylation 在 35 中的 19 个被观察(54.29%) 肿瘤样品。倡导者 methylation 肿瘤显示出低 WIF-1 蛋白质和 mRNA 表示,而倡导者 unmethylation 肿瘤显示了高蛋白质和 mRNA 表示层次。而且,, WIF-1 mRNA 表示的完全的缺席在四根房间线被观察有 demethylating 代理人的处理, 5-aza-2-deoxycytidine,恢复 WIF-1 表示。我们的结果建议 WIF-1 基因经常是在由异常倡导者 methylation 的星细胞瘤的 silenced。这可以是在星细胞瘤 carcinogenesis 的重要机制。
Wnt inhibitory factor-1 (WIF-1) acts as a Wnt antagonist and tumor suppressor, but hypermethylation of WIF-1 gene promoter and low expression of WIF-1 activate Wnt signaling aberrantly and induce the development of several human tumors. By using RT-PCR, immunohisto- chemistry and methylation-specific PCR, we analyzed the expression and methylation of WIF-1 in 4 normal brain tissues, 35 freshly resected astrocytoma tissues and 4 glioblastoma-derived cell lines. Significant downregulation of WIF-1 mRNA and protein expression levels was observed in astrocytoma tissues compared with normal brain tissues. Significant association between WIF-1 downregulation and pathological grade of astrocytomas was found. WIF-1 gene aberrant methylation was observed in 19 of 35 (54.29%) tumor samples. The promoter methylation tumors showed low WIF-1 protein and mRNA expression, whereas the promoter unmethylation tumors displayed high protein and mRNA expression levels. Moreover, complete absence of WIF-1 mRNA expression was observed in four cell lines, whereas treatment with demethylating agent, 5-aza-2'-deoxycytidine, restored WIF-1 expression. Our results suggested that the WIF-1 gene is frequently silenced in astrocytoma by aberrant promoter methylation. This may be an important mechanism in astrocytoma carcinogenesis.