In vitro expression of von Hippel-Lindau tumor suppressor gene in human renal cell carcinoma by Herpes simplex virus vector

单纯疱疹病毒载体在人肾细胞癌中体外表达von Hippel-Lindau抑癌基因

• 批准号: 07557105
• 负责人: SHUIN Taro
• 金额: $ 3.58万
• 依托单位: Kochi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557105/
• 关键词: Von Hippel-Lindau (VHL) disease; VHL tumor suppressor gene; transfection; Herpes Simplex virus vector ; Gene therapy; von Hippel-Lindau病遺伝子; HSVウイルス

Von Hippel-Lindau (VHL) disease is a multitumor syndrome which shows hemangioma of the retina, hemangiblastoma of the central nervous system, pheochromocytoma of the adrenal gland, and renal cell carcinoma of the kidney as major tumors. The responsible gene for this disease, the VHL tumor suppressor gene was identified at chromosome 3p25-26 in 1993. To make a good model system for the introduction of VHL gene into human cells, we examined the efficacy of Herpes Simplex virus (HSV) vector, which are usually used to express foreign genes in cells in the central nervous system (CNS), for human renal cell carcinoma cell. VHL gene was efficiently introduced and expressed in renal cell carcinoma cell lines and other CNS cancer cells with HSV vector. Introduced VHL gene is localized in the cytoplasm. The cell introduced with VHL gene showed growth inhibitory effect at shorter incubation period. However, HSV vector itself has some cytotoxic effects to the introduced kidney cancer cells after long incubation with HSV vector.

Von Hippel-Lindau（VHL）病是一种多肿瘤综合征，其主要肿瘤为视网膜血管瘤、中枢神经系统血管母细胞瘤、肾上腺嗜铬细胞瘤和肾脏肾细胞癌。1993年在染色体3 p25 -26上鉴定出了VHL肿瘤抑制基因，该基因是导致这种疾病的基因。为了建立一个良好的VHL基因导入人细胞的模型系统，我们研究了用于在中枢神经系统（CNS）细胞中表达外源基因的单纯疱疹病毒（HSV）载体对人肾细胞癌细胞的作用。用HSV载体将VHL基因导入肾癌细胞系和其他中枢神经系统肿瘤细胞中，并在其中高效表达。导入的VHL基因定位于细胞质中。导入VHL基因的细胞在较短的孵育时间内表现出生长抑制作用。然而，HSV载体本身在与HSV载体长时间孵育后对引入的肾癌细胞具有一定的细胞毒性作用。

项目成果

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