2005 Fiscal Year Final Research Report Summary
Restoration of RUNX3 enhances TGF-beta-dependent p21expression in a biliary tract cancer cell line
| Project/Area Number |
16590591
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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 | KYOTO university |
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Principal Investigator |
YAZUMI Shujiro Kyoto University Graduate School of Medicine, Deptartment.of Gastroenterology and Hepatology, Assistant professor, 医学研究科, 講師 (60332722)
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| Project Period (FY) |
2004 – 2005
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| Keywords | RUNX3 / TGF-beta signaling / p21 / Biliary tract cancer / FOXO3a |
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| Research Abstract |
Background and Aim : RUNK3 is a candidate tumor-suppressor gene localized in Ip36, a region commonly inactivated by deletion and methylation in various human tumors. The aim of this study was to elucidate the role of RUNX3 in TGF-β signaling in a biliary tract cancer cell line.
Materials and Methods : We transfected a biliary tract cancer cell line, Mz-ChA-2 cells, which do not express RUNX3 but have intact TGF-β receptor II and SMAD4, with the RUNX3 expression plasmid pcDNA3.1/RUNX3 or with the vector pcDNA3.1 as a control. The responses of the RUNK3-transfected cells and control cells (mock) to TGF-β stimulation were compared.
Results : Four Mz-ChA-2/RUNK3 clones and one control clone were obtained. Although TGF-β1 only slightly inhibited growth of the control cells, growth inhibition and TGF-β-dependent G1 arrest were significantly enhanced in the RUNK3-transfected clones. None of the clones, however, exhibited apoptosis. The slightly increased TGF-β1-induced p21 expression in the control clone, which was strongly enhanced in the RUAX3-transfected clones, was accompanied by augmented decreases in the expression of cyclins D1 and E. When RUNX3 siRNA was added, TGF-β-dependent induction of p21 was reduced in the RUNX3-transfected clones. Moreover, TGF-β-dependent FOXO3A induction was significantly enhanced in proportion to the expression levels of RUNX3 in the RUNX3-transfected clones. Xenografts of the clones in nude mice demonstrated that tumorigenicity was significantly decreased in the RUNK3-transfected clones in inverse proportion to the expression levels of RUNX3.
Conclusion : Restoration of RUNX3 expression enhanced TGF-β-dependent G1 arrest in association with up-regulation of p21 in a biliary tract cancer cell line. Thus, RUNX3 appears to be involved in TGF-β-induced expression of p21 and the resulting induction of TGF-β-dependent G1 arrest.
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[Journal Article] Frequent downregulation of the runt domain transcription factors RUNX1, RUNX3 and their cofactor CBFB in gastric cancer.2005
Author(s)
Sakakura C, Hagiwara A, Miyagawa K, Nakashuna S, Yoshikawa T, Kin S, Nakase Y, Ito K, Yamagishi H, Yazumi S, Chiba T, Ito Y.
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Journal Title
Int J Cancer. 113
Pages: 221-228
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Possible involvement of RUNX3 silencing in the peritoneal metastases of gastric cancers.2005
Author(s)
Sakakura C, Hasegawa K, Miyagawa K, Nakashuna S, Yoshikawa T, Kin S, Nakase Y, Yazumi, S Yamagishi H, Okanoue T, Chiba T, Hagiwara A.
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Journal Title
Chin Cancer Res. 11(18)
Pages: 6479-6488
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Frequent loss of RUNX3 gene expression in human bile duct and pancreatic cancer cell lines.2004
Author(s)
Wada M, Yazumi S, Takaishi S, Hasegawa K, Sawada M, Tanaka H, Ida H, Sakakura C, Ito K, Ito Y, Chiba T.
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Journal Title
Oncogene.
Pages: 2401-2407
Description
「研究成果報告書概要(欧文)」より
