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Study of ovarian carcinogenesis using mice models

Research Project

Project/Area Number 18591847
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionShowa University

Principal Investigator

OKUDA Tsuyoshi  Showa University, Obstetrics and Gynecology, Researcher (60407434)

Co-Investigator(Kenkyū-buntansha) SASAKI Nobuya  Hokkaido University, 獣医学研究科, Associate professor (20302614)
MAEDE Shin  Asahi Life Foundation, The Institute for Adult Diseases, researcher (40415956)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥4,040,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥540,000)
Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordsovarian carcinoma / beta cathenine / K-ras / OGP promoter / Cre recombinase / model mouse
Research Abstract

Overall aim : Define the role that multiple genetic change s and inflammation plays in promoting ovarian tumorigenesis.
Specific aim : 1) Establish the mice model system in ovary.2) Determine the role of K-ras and beta-cathenine in the development of mice model of ovarian cancer.3) Determine how NF-kappa B activation pathway influence to the development of ovarian cancer in mammalian system.
Study design: 1. Construction of mutant rake model of K-ras and beta-cathenine in ovary.
1) Construction of ovarian specific Cre recombinase TG mouse. 2) Construction of latent K-ras TG and beta-cathenine TG mouse. 3) Construction of ovarian specific K-ras TG and beta-cathenine TG mouse. 4) Determination of phenotype in mice.
2.Construction of NF kappa B KO and overexpression system in mice ovary.
1)Construction of ovarian specific NF kappaB KO mouse.2)Construction of ovarian specific NF kappaB overexpression mouse.3)Determination of phenotype in mice.
Result 1. Mouse ovarian specific promoter (OGP promo … More ter) was cloned upstream of Cre recombinase gene and transferred into pBS SK(+). The DNA construct was injected into mouse embryo. Three positive strains were obtained and examined to determine the ovarian specific expression of Cre recombinase. At present, the positive expression is not obtained. 2)Mutant exon of beta-cathenine was cloned and placed downstream of CAG promoter, loxP , CAT and loxP sequence and transferred into pBS SK(+).The DNA construct was injected into mouse embryo. One of a strain expressed sutuffer neo in ovary. Using an adeno virus gene delivery technique for the introduction of Cre recombinase into mouse ovary, beta-cat TG was revealed to express cre recombinase in ovarian cells. This system will be used until OGP-Cre system is established. Mutant exon of K-ras was cloned and placed downstream of CAG promote, loxP , CAT and loxP sequence and transferred into pBS SK(+).The DNA construct was injected into mouse embryo.2.Adeno-Cre was injected into the maw oflKKbeta KO mouse. After the confirmation of IKKbeta deletion in ovary phenotyping analysis will be evaluated. Less

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (16 results)

All 2007 2006

All Journal Article (13 results) Presentation (3 results)

  • [Journal Article] Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production2007

    • Author(s)
      Naugler WE, Sakurai T, Kim S, Maeda S, Kim K, Elsharkawy AM, Karin M
    • Journal Title

      Science 317・5834

      Pages: 121-124

    • Related Report
      2007 Annual Research Report
  • [Journal Article] A large noncoding RNA is a marker for murine hepatocellularcarcinomas and a spectrum of human carcinomas2007

    • Author(s)
      Lin R, Maeda S, Liu C, Karin M, Edgington TS
    • Journal Title

      Oncogene 26・6

      Pages: 851-858

    • Related Report
      2007 Annual Research Report
  • [Journal Article] A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas2007

    • Author(s)
      Lin R, Maeda S, Liu C, Karin M, Edgington TS
    • Journal Title

      Oncogene 26・6

      Pages: 851-8

    • Related Report
      2006 Annual Research Report
  • [Journal Article] DNA polymerase zeta accout for the reduced cytotoxicity and enhanced mutagenicity of cisplatin in human colon carcinoma cells that have lost DNA mismatch repair2006

    • Author(s)
      Lin X, Trang J, Okuda T, Howell S
    • Journal Title

      Clinical Cancer Res 12

      Pages: 563-568

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Human REV1 Modulates the Cytotoxicity and Mutagenicity of Cisplatin in Human Ovarian Carcinoma Cells2006

    • Author(s)
      Lin X, Okuda T, Trang J, Howell S
    • Journal Title

      Mol Pharmacol 69

      Pages: 1748-1754

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Loss of hepatic NF-kappa B activity enhances chemical hepatocarcinoge nesis through sustained c-Jun N-terminal kinase 1 activation2006

    • Author(s)
      Sakurai T, Maeda S, Chang L, Karin M
    • Journal Title

      Proc Natl Acad Sci U S A 103

      Pages: 10544-51

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Human REV1 Modulates the Cytotoxicity and Mutagenicity of Cisplatin in Human Ovarian Carcinoma Cells2006

    • Author(s)
      Lin, X, Okuda, T, Trang, J, Howell, S
    • Journal Title

      Mol Pharmacol 69-5

      Pages: 1748-1754

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] DNA polymerase zeta accout for the reduced cytotoxicity and enhanced mutagenicity of cisplatin in human colon carcinoma cells that have lost DNA mismatch repair2006

    • Author(s)
      Lin, X, Trang, J, Okuda, T, Howell, S
    • Journal Title

      Clinical Cancer Res 12-2

      Pages: 563-568

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Loss of hepatic NP-kappa B activity enhances chemical hepatocarcinogenesis through sustained c-Jun N-terminal kinase 1 activation2006

    • Author(s)
      Sakurai, T, Maeda, S, Chang, L, Karin, M
    • Journal Title

      Proc Natl Acad Sci U S A 103-28

      Pages: 10544-51

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Human REV1 Modulates the Cytotoxicity and Mutagenicity of Cisplatin in Human Ovarian Carcinoma Cells2006

    • Author(s)
      Lin X, Okuda T, Trang J, Howell SB
    • Journal Title

      Mol Pharmacol 69・5

      Pages: 1748-1754

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Department of Medicine and the Cancer Center, University of California, San Diego, La Jolla, California2006

    • Author(s)
      Lin X, Trang J, Okuda T, Howell SB
    • Journal Title

      Clinical Cancer Res 12・2

      Pages: 563-568

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Loss of hepatic NF-kappa B activity enhances chemical hepatocarcinogenesis through sustained c-Jun N-terminal kinase 1 activation2006

    • Author(s)
      Sakurai T, Maeda S, Chang L, Karin M
    • Journal Title

      Proc Natl Acad Sci U S A 103・28

      Pages: 10544-51

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The E3 ubiquitin ligase itch couples JNK activation to TNFalpha-induced cell death by inducing c-FLIP(L) turnover2006

    • Author(s)
      Chang L, Kamata H, Solinas G, Luo JL, Maeda S, Venuprasad K, Liu YC, Karin M
    • Journal Title

      Cell 124・3

      Pages: 601-13

    • Related Report
      2006 Annual Research Report
  • [Presentation] 卵巣癌細胞におけるhREVI発現抑制によるプラチナ耐性獲得の減少2007

    • Author(s)
      奥田 剛、千葉 博、満川 香織、長塚 正晃、岡井 崇
    • Organizer
      第59回日本産科婦人科学会総会・学術講演会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2007-04-16
    • Related Report
      2007 Annual Research Report
  • [Presentation] hREV1 modulates the cytotoxicity and mutagenicity of cisplatin in human ovarian carcinoma cells2006

    • Author(s)
      Lin X, Okuda T, Trang J, Howell S
    • Organizer
      97th Annual Meeting of American Association for Cancer Research
    • Place of Presentation
      アメリカ合衆国
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] hREV1 modulates the cytotoxicity and mutagenicity of cisplatin in human ovarian carcinoma cells2006

    • Author(s)
      Xinjian, Lin, Tsuyoshi, Okuda, Julie, Trang, Stephen, B, Howell
    • Organizer
      97th Annual Meeting of American Association for Cancer Research
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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