Neogenin表达下调与神经胶质瘤发生、发展的关系  

Downregulation of Neogenin in the Carcinogenesis and Progression of Glioma

作　　者：吴新民[1] 赵刚[1] 许万震[2] 万茜淋[2] 曹让娟[3] 李蕴潜[1] 朱筱娟[3] 

机构地区：[1]吉林大学第一医院神经肿瘤外科,吉林长春130021 [2]哈尔滨医科大学附属第四医院神经外科,黑龙江哈尔滨150001 [3]东北师范大学细胞遗传所教育部分子遗传学重点实验室,吉林长春130024

出　　处：《中国神经肿瘤杂志》2013年第1期8-14,共7页Chinese Journal of Neuro-Oncology

摘　　要：背景与目的:神经胶质瘤是中枢神经系统最常见肿瘤,其发病机制尚不明确。Neogenin表达异常与多种癌症进展及预后相关,是一个潜在的肿瘤抑制因子。本研究的目的在于阐明Neogenin在神经胶质瘤发生和进展过程中的作用。方法:通过对小鼠正常脑组织及人神经胶质瘤组织及肿瘤周边脑组织进行免疫组织化学方法染色,分析Neogenin在正常脑组织及肿瘤组织中的细胞内分布差异,以及其在胶质瘤中表达水平较其周边脑组织表达的差别;进一步分析其在不同级别胶质瘤中的表达水平差异;最后通过MSP法分析Neogenin在神经胶质瘤中的启动子甲基化水平。结果:我们发现Neogenin在小鼠脑中表达丰富,主要位于神经胶质细胞的胞膜上;Neogenin在肿瘤区域的平均表达水平较周边区域低,其在肿瘤区域主要胞浆内呈弥散分布。对69例原发胶质瘤患者的肿瘤组织进行免疫组织化学分析,进一步确认了Neogenin在神经胶质瘤中表达水平与肿瘤的恶性程度呈负相关(One-Way ANOVA,n=69,P<0.01)。通过甲基化特异性PCR法分析表明,Neogenin的启动子在37.5%(3/8)的人神经胶质瘤组织中存在甲基化,但是我们在3株人脑胶质瘤细胞系中未检测到Neogenin启动子甲基化现象。结论:Neogenin与神经胶质瘤的发生、发展有关,其启动子部分甲基化可能是导致Neogenin表达下调的原因之一,这种表达下调为神经胶质瘤的起源、发展提供了选择性优势。BACKGROUND ＆ OBJECTIVE： Glioma is the most common group of primary brain tumor. Neogenin is well known for its fundamental role in axon guidance and also a dependence receptor regarded as a tumor inhibitor in carcinogenesis. While neogenin＇s paucity hasbeen reported in variety of cancers, its relationship with glioma remains unclear. In this study, we explored the correlation between them. METHODS： Immunohistochemistry was employed to detect the expression of Neogenin in mouse brain, human glioma andsurrounding normal brain. Methylation-specific PCR was used to identify the methylation status of the promoter of Neogenin in glioma tissues. RESULTS： Neogenin was highly expressed in mouse embryo brain and normal human brain tissues and located along the cell membrane. Western blot analysis showed that expression of neogenin was lower in glioma tissues than in their matching surrounding normal brain tissues. By using immunohistochemical assay, we showed that neogenin was down-regulated while the grade of glioma aggravated （One-Way ANOVA, n=69, P〈 0.01）. With methylation-specific PCR assay, we reported that the promoter of neogenin was methylated in 37.5% gliomas （3/8）, but methylation was absent in 3 established glioma cell lines. CONCLUSION： Our results demonstrated that downregulation of neogenin in gliomas is an advantage for glioma tumorigenesis and progression.

关 键 词：NEOGENIN 神经胶质瘤 肿瘤发生 发展 甲基化 

分 类 号：R739.41[医药卫生—肿瘤]