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Analysis of von Hippil-Lindau (VHL) gene in Human Renal Cancer

人肾癌中 von Hippil-Lindau (VHL) 基因的分析

基本信息

批准号：
14571503
负责人：
KASAHARA Kotaro
金额：
$ 2.56万
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 (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571503/
关键词：
cytoskeletal VHL microarray temperature receptivity 腎細胞癌 VHL遺伝子ストレス蛋白

项目摘要

Mutation of the von Hippel-Lindau (VHL) gene is responsible for familial and sporadic renal cell carcinomas as well as for cancers in many other organs. According to recent studies, the VHL protein (pVHL) is a multifunctional tumor suppressor protein associated with the inhibition of angiogenesis, cell cycle exit, fibronectin matrix assembly, and proteolysis. To examine whether pVHL affects other important cellular events such as morphogenesis, adhision, cytoskeletal organization, or motility, we introduced the VHL gene into human kidney and lung cancer cells and compared its effects with those in parental cells. Compared with non-pVHL-expressing cells, the morphogenesis of pVHL-expressing cells was remarkably changed, with cells having many focal adhesions and stress fibers and a spreading morphology. The attachment ability of non-pVHL-expressing cells was significantly increased by expression of pVHL. Additional studies showed that vinculin was translocalized from the cytoplasm to the cell membrane by the pVHL expression, indicating induction of focal adhesion formation by pVHL. Furhtermore, motility of the pVHL-expressing cells was significantly reduced compared with that of non-pVHL-expressing cells (P<0.05). These results indicate that pVHL stabilized actin organization and inhibited cell motility through focal adhesion formation. Thus, pVHL plays a crucial rold in cytoskeletal organization and motility and functions as a unique suppressor protein in malignant cells.

von Hippel-Lindau（VHL）基因的突变是家族性和散发性肾细胞癌以及许多其他器官癌症的原因。根据最近的研究，VHL蛋白（pVHL）是一种多功能肿瘤抑制蛋白，与抑制血管生成，细胞周期退出，纤连蛋白基质组装和蛋白水解有关。为了研究pVHL是否影响其他重要的细胞事件，如形态发生，粘附，细胞骨架组织，或运动性，我们引入VHL基因到人肾癌和肺癌细胞，并比较其效果与亲本细胞。与不表达pVHL的细胞相比，表达pVHL的细胞的形态发生发生显著改变，细胞具有许多粘着斑和应力纤维以及铺展形态。非pVHL表达细胞的附着能力通过pVHL的表达而显著增加。另外的研究表明，黏着斑蛋白通过pVHL表达从细胞质转移到细胞膜，表明pVHL诱导粘着斑形成。表达pVHL的细胞运动能力明显低于不表达pVHL的细胞（P<0.05）。这些结果表明，pVHL稳定肌动蛋白的组织和抑制细胞运动通过粘着斑的形成。因此，pVHL在细胞骨架组织和运动中起着至关重要的作用，并在恶性细胞中作为一种独特的抑制蛋白发挥作用。

项目成果

期刊论文数量（24）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Recent advances in ideas on the molecular pathology and clinical aspects of Von Hippel-Lindau disease.

冯·希佩尔-林道病的分子病理学和临床方面的最新进展。

DOI：
发表时间：
2004
期刊：
Int J Clin Oncol 9・(4)
影响因子：
0
作者：
Guo H;Takahashi S;Cho S;Hera T;Tomiyasu S;Sumikawa K;Tokinaga K;Ishimura H;Takahashi T;Shuin T
通讯作者：
Shuin T

The prognostic value of angiogenesis and metastasi-related genes for progression of transitional cell carcinoma of the renal pelvis and ureter.

血管生成和转移相关基因对肾盂和输尿管移行细胞癌进展的预后价值。