| Project/Area Number |
09670590
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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 |
Gastroenterology
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| Research Institution | Japanese Foundation for Cancer Research |
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Principal Investigator |
KAWABATA Masahiro The Cancer Institute, Biochemistry Associate Member, 癌研究所・生化学部, 主任研究員 (60224838)
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| Co-Investigator(Kenkyū-buntansha) |
HANAI Jun-ichi The Cancer Institute, Biochemistry Associate, 癌研究所・生化学部, 研究員 (70261964)
KATO Mitsuyasu The Cancer Institute, Biochemistry Associate, 癌研究所・生化学部, 研究員 (20194855)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1998: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | TGF-beta / DPC4 / Smad / colorectal cancer / Drosophila |
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| Research Abstract |
(1) We identified novel Drosophila Smads, Medea and dSmad2.We proved, through the biochemical characterization of these Smads, that the signaling pathway by Smads is conserved between Drosophila and mammals.
(2) Smad2 and Smad3 exist as monomers m the absence of TGF-beta stimulation, and form homo- and hetero-oligomers with Smad4 upon phosphorylation by TGF-beta receptor.Both homomeric and hetero-meric Smad3 were capable to bind to DNA.
(3) A mutation of Smad2 found in colorectal cancers was introduced to the corresponding position in Smad3.The mutant Smad3 interfered with the phosphorylation of the wild type Smad2 and Smad3, thereby inhibiting the transactivation and growth inhibition of HaCat cells by TGF-beta.Thus the mutation not only disrupts the normal function of Smads, but is likely to positively contributes to the car-cinogenesis in a dominant-negative fashion.
(4) We identified a germline mutation of the TGF-beta type II receptor gene in RER-negative hereditary non-polyposis colorectal cancer (HNPCC), which generalizes that TGF-beta suppresses the colorectal carcinogenesis.
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