Role of VHL tumor suppressor gene in central nervous system

VHL抑癌基因在中枢神经系统中的作用

• 批准号: 09671435
• 负责人: KANNO Hiroshi
• 金额: $ 1.86万
• 依托单位: Yokohama City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671435/
• 关键词: von Hippel-Lindau disease; Central nervous system; Hemangioblastoma; DNA diagnosis; Neuronal differentiation; クォン・ヒッペル・リンド-病; 腫瘍抑制遺伝子; 母斑病; 遺伝性脳腫瘍

Von Hippel-Lindau disease (VHL) is an autosomal dominant hereditary disease which develops hamangioblastomas in the central nervous system and retina, renal cell carcinoma, and pheochromocytoma. The causative gene has been isolated from chromosome 3p in 1993. We have found somatic VHL gene mutations in not only sporadic hemangioblastomas and renal cell but also gliomas. In addition, we have performed molecular genetic diagnosis of 80 Japanese VHL families by the DNA analyses. The expressions of VHL gene and product were identified at neuron in the central nervous system and proximal renal tubule as well as cytoplasm of hemangiobalstoma and glioma. However, pathologically more malignant gliomas showed less expression of VHL gene produst. In process of neuronal development, VHL gene expressions were correlated with neuronal differentiation in neural stem cells. In addtion, it was suggested that cell cycle of neural stem cells were down-regulated by VHL gene.

Von希佩尔-林道病（VHL）是一种常染色体显性遗传病，可发展为中枢神经系统和视网膜的成网状细胞瘤、肾细胞癌和嗜铬细胞瘤。1993年从染色体3p中分离出致病基因。我们不仅在散发性血管母细胞瘤和肾细胞中发现了体细胞VHL基因突变，而且在胶质瘤中也发现了体细胞VHL基因突变。此外，我们还通过DNA分析对80个日本VHL家族进行了分子遗传学诊断。VHL基因及其产物在中枢神经系统神经元和肾近端小管以及血管母细胞瘤和胶质瘤的细胞质中表达。而病理上越恶性的胶质瘤VHL基因前体表达越少。在神经元发育过程中，VHL基因的表达与神经干细胞的神经元分化有关。此外，还提示VHL基因下调了神经干细胞的细胞周期。

项目成果

Kanno H, Yamamoto I, Yao M, Shuin T: "von Hippel-Lindau disease" Brain and Nerve. 51. 33-40 (1999)

Kanno H、Yamamoto I、Yao M、Shuin T：“von Hippel-Lindau 病”大脑和神经。

菅野洋: "脳病変とvon Hippel-Lindau病" 病理と臨床. 15・2. 129-133 (1997)

菅野浩：“脑损伤和 von Hippel-Lindau 病”病理学和临床研究 15・2（1997 年）。

Kanno H, Shain T, Kondo K, et al: "Somatic mutations of the von Hippel-Lindau tumor suppressor gene and loss of heterozygosity on chrosome 3p in human glial tumors" Cancer Research. 57. 1035-1038 (1997)

Kanno H、Shain T、Kondo K 等人：“人类胶质瘤中 von Hippel-Lindau 肿瘤抑制基因的体细胞突变和染色体 3p 杂合性丢失”癌症研究。

Kanno H, Shuin T,Kondo K,et al.: "Somatic mutations of the von Hippel-Lindau tnnor suppressor gene and loss of hetero zygosity on chromosome 3p in human glial tumors" Cancer Research. 57. 1035-1038 (1997)

Kanno H、Shuin T、Kondo K 等人：“人类胶质瘤中 von Hippel-Lindau tnnor 抑制基因的体细胞突变和染色体 3p 杂合性缺失”癌症研究。

菅野洋, 矢尾正祐, 執印太郎: "腫瘍性病変の神経科学、神経皮膚症候群の遺伝子病態/von Hippel-Lindau病" 株式会社メジカルビュー社, 290 (1998)

Hiroshi Kanno、Masuke Yao、Taro Shiku：“肿瘤病变的神经科学、神经皮肤综合征/冯·希佩尔-林道病的遗传病理学”Medical View Inc.，290 (1998)