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

Von Hippel-Lindau(VHL)基因突变与家族性和散发性肾细胞癌以及许多其他器官的癌症有关。根据最近的研究，VHL蛋白(PVHL)是一种多功能的肿瘤抑制蛋白，与抑制血管生成、细胞周期退出、纤维连接蛋白基质组装和蛋白降解有关。为了检测pVHL是否影响其他重要的细胞事件，如形态发生、黏附、细胞骨架组织或运动，我们将VHL基因导入人肾和肺癌细胞，并将其作用与亲本细胞中的作用进行比较。与不表达pVHL的细胞相比，表达pVHL的细胞的形态发生了显著的变化，细胞有大量的局灶性粘连和应力纤维，形态呈铺展状。PVHL的表达可显著提高非pVHL表达细胞的黏附能力。进一步的研究表明，pVHL的表达使纽蛋白从细胞质转位到细胞膜，表明pVHL诱导局部黏附的形成。此外，表达pVHL的细胞的活力明显低于不表达pVHL的细胞(P&lt；0.05)。这些结果表明，pVHL通过局部黏附形成稳定了肌动蛋白的组织，抑制了细胞的运动。因此，pVHL在细胞骨架的组织和运动中起着至关重要的作用，并在肿瘤细胞中作为一种独特的抑制蛋白发挥作用。

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.