| Project/Area Number |
12213009
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Tohoku University |
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Principal Investigator |
NODA Tetsuo Tohoku Univ School of Medicine, Professor, 大学院医学系研究科, 教授 (10183550)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Akira AkirUniv School of Medicine, Professor, 医学部, 教授 (10311565)
TAKANO Hiroshi Tohoku Univ, School of Medicine, Research Associate, 大学院医学系研究科, 助手 (00241555)
YAGINUMA Katsuyuki Cancer Institute, Dept of Cell Biology, Associatie, 癌研究所細胞生物部, 研究員 (40182307)
KAMIJO Takehiko Shinshu Univ, School of Medicine, Associatie Proffessor, 医学部, 講師 (90262708)
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| Project Period (FY) |
2000 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥227,700,000 (Direct Cost: ¥227,700,000)
Fiscal Year 2004: ¥48,500,000 (Direct Cost: ¥48,500,000)
Fiscal Year 2003: ¥48,600,000 (Direct Cost: ¥48,600,000)
Fiscal Year 2002: ¥42,600,000 (Direct Cost: ¥42,600,000)
Fiscal Year 2001: ¥50,000,000 (Direct Cost: ¥50,000,000)
Fiscal Year 2000: ¥38,000,000 (Direct Cost: ¥38,000,000)
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| Keywords | Patched / β-catenin / APC / PTEN / ジーンターゲティング / 癌抑制遺伝子 / SMAD4遺伝子 / VHL遺伝子 / ARF遺伝子 / PTEN遺伝子 / ノックアウトマウス / p53遺伝子 |
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| Research Abstract |
In this project, using technologies of mouse reverse genetics including a conditional gene targeting in mice, we have performed functional analyses on many cancer-related genes, such as tumor suppressor genes and oncogenes. Especially, functions of cancer related genes involved in Wnt, Sonic Hedgehog and PIP3 signaling pathways were intensely analyzed. Through these studies, we have succeeded to show substantial amount of evidence for molecular mechanisms regulating the process of carcinogenesis in vivo. In addition, we have also succeeded in establishing several ideal models `for human carcinogenesis : For example, we could clearly show that the inactivation of Patched-1 in outer germinal layer cells of developing cerebellum may suppress their growth arrest resulting in the formation of medulloblastoma in cerebellum. We could also show that Pten may actually function as a negative regulator of PiP3 pathway in varied tissues in mice, such as T cells, keratinocytes, hepatocytes and epithelias cells of prostate, and Pten inactivation actually induced tumors in these tissues. These information may greatly contribute for elucidation of molecular mechanisms of human carcinogenesis.
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