Elucidation in the mechanism of human renal cell carcinoma cancer growth and micrometastasis with inactivation of VHL
| Project/Area Number |
14370515
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 University School of Medicine |
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Principal Investigator |
SHUIN Taro Kochi University, school of medicine, Professor, 医学部, 教授 (80179019)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Keiji Kochi University, school of medicine, Assistant Professor, 医学部附属病院, 講師 (00294827)
OKUDA Heiwa Kochi University, school of medicine, Research Associate, 医学部, 助手 (60325420)
KAMADA Masayuki Kochi University, school of medicine, Research Associate, 医学部附属病院, 助手 (90304683)
ASO Teijiro Kochi Universith, school of medicine, Professor, 医学部, 教授 (20291289)
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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 |
¥11,400,000 (Direct Cost: ¥11,400,000)
Fiscal Year 2003: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥7,800,000 (Direct Cost: ¥7,800,000)
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| Keywords | tumor suppressor gene / methylation / renal cell carcinoma / VHL gene / VEGF / MIRC9 / Hypoxia Inducible Factor / メチル化 / CpG island methylator phenotype / VHL / Ubiquitin liagase |
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| Research Abstract |
Since human renal cell carcinoma (RCC) is resistant against chemotherapy or radiation therapy, there is no definitive curable treatment for the advanced RCC or its distant metastasis. Several cytokines shows only minor effect. Human clear cell RCCs compose of 80% of whole human RCCs. It is well known that von Hippel-Lindau (VHL) disease gene is mutated and inactivated in 70% of human clear cell RCCs. VHL protein makes complex with ElonginB & C to VBC complex in normal cells and works as ubiquitin ligase. It ubiquitates hypoxia inducible factor (HIF) at normoxic condition. HIF is degradeted at proteasome. When VHL gene is inactivated, HIF is upregulated at normoxic condition. This condition result in the high level of HIF, thereby overproduction of VEGF or Glucose transporter. That causes in a good condition for human RCCs. However, this condition itself is not sufficient for the explanation of the tumor development for human RCCs. We tried to detect methylated and inactivated possible tumor suppressor genes in human RCCs, which explains tumor development and growth together with inactivation of VHL. Several genes such as RASSF1A, CHFA, CACNA1G, TMS1,Cox2,DAPK, MINT, MINT2,MIRC9,MIRC37 are methylated and inactivated in human clear cell RCCs in Japan at different kind of extent. Similar findings are obtained in human clear cell lines. Therefore it is regarded that inactivation of the VHL gene with these genes are responsible for the development of human RCCs. Several pathways such as, HIF, VEGF, and Elongin are involved for the development and progression of human clear cell RCCs.
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Report
(3 results)
Research Products
(12 results)
