| Project/Area Number |
14571503
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Kochi Medical School |
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Principal Investigator |
KASAHARA Kotaro Kochi University, Kochi Medical School, Research Associate, 医学部附属病院, 助手 (80315001)
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| Co-Investigator(Kenkyū-buntansha) |
YAMASAKI Ichiro Kochi University, Kochi Medical School, Research Associate, 医学部附属病院, 助手 (40315015)
INOUE Keiji Kochi University, Kochi Medical School, Assistant Professor, 医学部附属病院, 講師 (00294827)
SHUIN Taro Kochi University, Kochi Medical School, Professor, 医学部, 助手 (80179019)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | cytoskeletal / VHL / microarray / temperature receptivity / 腎細胞癌 / VHL遺伝子 / ストレス蛋白 |
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| Research Abstract |
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.
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