| Project/Area Number |
13670537
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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 | Sapporo Medical University |
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Principal Investigator |
TERUI Takeshi Sapporo Medical University, School of Medicine, Assistant Professor, 医学部, 助手 (50281233)
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| Co-Investigator(Kenkyū-buntansha) |
KATO Junji Sapporo Medical University, School of Medicine, Assistant Professor, 医学部, 助教授 (20244345)
古川 勝久 札幌医科大学, 医学部, 講師 (60244349)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Contact Inhibition / γ-Catenin / p21 / WAF1 / Rho / 消火器癌 / 細胞増殖抑制 / E-カドヘリン / カテニン / WAF-1 / 消化器癌 / E-ガドヘリン |
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| Research Abstract |
To investigate the mechanism of contact inhibition, we cloned an adhesive subline HSC39Ad from parental non-adhesive HSC39 gastric cancer cell line, which has a deletion in the β-catenin gene (Mol Cell Biol 1995 Mar : 15(3) : 1175-81). This subline grew slower than the parental cells in vitro and in vivo. The neutralizing antibody of E-cadherin (HECD1) caused the lost of adhesive character of HSC39Ad cells, resulting in the enhancement of growth rate and the decrement of the expression of both p21/WAF1 and Rb in the dephosphorylated form. The same results were obtained by the specific antisense oligonucleotide against γ-catenin, which was expressed in HSC39Ad two-times higher than HSC39 cells. On the other hand, the treatment of HSC39Ad cells with HECD1 caused the activation of the small GTP-binding protein Rho. Further, C3, the inhibitor of Rho, restored both the enhancement of growth rate and the decrement of the expression of p21/WAF1 induced by HECD1 in HSC39 Ad cells. These results indicate that β-catenin bound with E-cadherin causes the signal transduction via Rho to p21/WAF1, resulting in the contact inhibition of HSC39 cells.
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