2004 Fiscal Year Final Research Report Summary
Fuctinonal analysis of cancer related genes by targeted mutagenesis in mice
| 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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| Keywords | Patched / β-catenin / APC / PTEN |
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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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[Journal Article] Oligo-astheno-teratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta2004
Author(s)
T.Nakamura, R.Yao, T.Ogawa, T.Suzuki, C.Ito, N.Tsunekawa, K.Inoue, R.Ajima, T.Miyasaka, Y.Yoshida, A.Ogura, K.Toshimori, T.Noce, T.Yamamoto, T.Noda.
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Journal Title
Nature Genetics 36(5)
Pages: 528-533
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas2004
Author(s)
Y.Horie, A.Suzuki (equal first, corresponding author).E.Kataoka, T.Sasaki, K.Hamada, J.Sasaki, K.Mizuno, G.Hasegawa, H.Kishimoto, M.lizuka, M.Naito, K.Enomoto, S.Watanabe, T.W.Mak, T.Nakano.
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Journal Title
J.Clin.Invest 113(12)
Pages: 1774-1783
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Apoptosis in neural crest Cells by functional loss of APC tumor suppressor gene2002
Author(s)
S.Hasegawa, T.Sato, H.Akazawa, H.Okada, A.Maeno, M.Ito, Y.Sugitani, H.Shibata, J.Miyazaki, M.Katsuki, Y.Yamauchi, K.Yamamura, S.Katamine, T.Noda.
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Journal Title
Proc.Natl.Acad.Sci.USA 99(1)
Pages: 297-302
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Lack of acrosome formation in mice lacking a Golgi protein, GOPC2002
Author(s)
R.Yao, C.Ito, Y.Natsume, Y.Sugitani, H.Yamanaka, S.Kuretake, K.Yanagida, A.Sato, K.Toshimori, T.Noda.
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Journal Title
Proc.Natl.Acad.Sci.USA 99(17)
Pages: 11211-11216
Description
「研究成果報告書概要(欧文)」より
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