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Comparison of the frequency of mtDNA mutation in primary and metastatic lesions of human malignant tumors

Research Project

Project/Area Number 21590349
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionChiba Cancer Center (Research Institute)

Principal Investigator

KOSHIKAWA Nobuko  千葉県がんセンター(研究所), 研究局, 研究員 (90260249)

Co-Investigator(Renkei-kenkyūsha) TAKENAGA Keizo  島根大学, 医学部・生命科学講座腫瘍生物学, 准教授 (80260256)
Research Collaborator HAYASHI Jun-ichi  筑波大学, 生命環境科学研究科(系), 教授 (60142113)
OHIRA Miki  千葉県がんセンター(研究所), 研究局, 研究員 (20311384)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsmtDNA変異 / 肺癌 / 大腸癌 / 原発巣 / 転移巣 / 神経膠腫 / 髄液播種 / ラマンバンド / ROS / 転移能 / 肺癌・大腸癌 / 癌部と非癌部 / 神経膠芽腫 / mtDNA / 変異 / ヒト腫瘍
Research Abstract

We showed that ROS-generating pathogenic mutations in NADH dehydrogenase subunit 6(ND6) gene of mitochondrial DNA(mtDNA), which is a subunit of complex I of the electron transport chain, can regulate tumor cell metastasis in mouse models. In this study, we compared the status of mutations and nonsynonymous single nucleotide polymorphisms(SNPs) of the genes encoding complex I subunits(ND1, ND2, ND3, ND4L and ND6) between primary and metastatic lesions of human lung and colon carcinomas. The combined frequency of appearance of nonsynonymous SNPs and mutations related to mtDNA base substitution disease such as LHON and novel mutations of Grantham value> 50 in the genes encoding complex I was considerably higher in metastatic lesions than in primary lesions. It may be possible that such mtDNA SNPs and mutations contribute to metastasis in human cancers.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (12 results)

All 2010 2009 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (5 results) Remarks (2 results)

  • [Journal Article] MCL-1V, a novel mouse antiapoptotic MCL-l variant, generated by RNA splicing at a non-canonical splicing pair.2010

    • Author(s)
      Kojima S, Hyakutake A, Koshikawa N, Nakagawara A, Takenaga K
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 391 Pages: 492-497

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reactive oxygen speciesgenerating mitochondrial DNA mutation up-regulates hypoxia-inducible factor-1 alpha gene transcription via phosphatid ylinositol 3-kinase-Akt/protein kinase C/histone deacetylase pathway2009

    • Author(s)
      Koshikawa N, Hayashi J, Nakagawara A, Takenaga K
    • Journal Title

      Journal of Biological Chemistry

      Volume: 284 Pages: 33185-33194

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] MCL-1V, a novel m ouse antiapoptotic MCL-1 variant, genera ted byRNA splicing at a non-canonical splicing pair2009

    • Author(s)
      Kojima S, Hyakutake A, Koshikawa N, Nakagawara A, Takenaga K
    • Journal Title

      Biochem BiophysRes Comun3

      Volume: 91 Pages: 492-497

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Reactive oxygen species-generating mitochondrial DNA mutation up-regulates hypoxia-inducible factor-lalpha gene transcription via phosphatidylinositol 3-kinase-Akt/protein kinase C/histone deacetylase pathway2009

    • Author(s)
      Koshikawa N, Hayashi J, Nakagawara A, Takenaga K
    • Journal Title

      Joarnal of Biological Chemistry 284

      Pages: 33185-33194

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MCL-1V, a novel mouse antiapoptotic MCL-1 variant, generated by RNA splicing at a non-canonical splicing pair2009

    • Author(s)
      Kojima S, Hyakutake A, Koshikawa N, Nakagawara A, Takenaga K
    • Journal Title

      Biochem Biophys Res Common. 391

      Pages: 492-497

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] ヒト肺癌及び大腸癌の原発巣と転移巣におけるmtDNA変異頻度2010

    • Author(s)
      越川信子、木村秀樹、飯笹俊彦、井内俊彦、滝口伸浩、竹永啓三、中川原章
    • Organizer
      第19回日本癌病態治療研究会
    • Place of Presentation
      東京
    • Year and Date
      2010-06-30
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] 低酸素、ミトコンドリアとがんの転移2009

    • Author(s)
      竹永啓三
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-03
    • Related Report
      2011 Final Research Report
  • [Presentation] ヒト肺がんおよび大腸がんの原発巣と転移巣におけるmtDNA変異頻度の比較2009

    • Author(s)
      越川信子、木村秀樹、飯笹俊彦、井内俊彦、滝口伸浩、秋元美穂、本間良夫、竹永啓三
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-03
    • Related Report
      2011 Final Research Report
  • [Presentation] 低酸素, ミトコンドリアとがんの転移2009

    • Author(s)
      竹永啓三(連携研究者)
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2009-10-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] ヒト肺がんおよび大腸がんの原発巣と転移巣におけるmtDNA変異頻度の比較2009

    • Author(s)
      越川信子
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2009-10-03
    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.chiba-cc.jp/inst/jp/index.html

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.chiba-cc.jp/inst/jp/index.html

    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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