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2010 Fiscal Year Annual Research Report

エピジェネティック疫学の疾病予防への応用

Research Project

Project/Area Number 20390169
Research InstitutionTokyo Medical and Dental University

Principal Investigator

湯浅 保仁  東京医科歯科大学, 大学院・医歯学総合研究科, 教授 (80111558)

Keywords胃がん / DNA / メチル化 / 血球DNA / エピジェネティクス
Research Abstract

(1)血球DNAのメチル化とがん化との関連およびメチル化に関与する要因の解析
血液白血球DNAのメチル化の程度を定量的に測定し、がんのバイオマーカーになりうるか、さらに生活習慣がメチル化にどう影響するかを明らかにする研究を行った。性・年齢をマッチさせた胃がん患者(Case)と非がんコントロール(Control)、各299名の血液白血球DNAについて、がん抑制遺伝子TUSC3と、がん促進的なIGF2遺伝子の定量的メチル化解析を行った。TUSC3のメチル化はCaseの方がControlより高く、高齢者と喫煙者ではメチル化が高かった。また、ピロリ菌抗体陽性者は陰性者よりメチル化値が高かった。一方、IGF2のメチル化はCaseの方がControlより低く、高齢者と喫煙者ではメチル化が低かった。以上から血液白血球DNAのメチル化程度は、がんのバイオマーカーになりうる可能性があり、さらに生活習慣により変化することが示唆された。
(2)マイクロRNA miR-181cのエピジェネティックな発現抑制と胃がんとの関連
胃がんにおけるマイクロRNA(以下miRNA)の発現低下とメチル化との関連性を明らかにするため、脱メチル化剤処理した胃がん細胞株を用いて、miRNAの発現プロファイルを調べた。その結果、miR-181cとmiR-432の2つに着目した。RT-PCR法によりmiR-181cは、複数の胃がん細胞株で脱メチル化剤処理による発現増加が認められた。miR-181cは、原発性胃がん組織16例のうち9例で発現が低下していた。miR-181cの機能を検討したところ、Precursor-miR-181cを導入した2つの細胞株で細胞増殖が低下した。cDNAアレイによりmiR-181cの標的遺伝子の探索を行ったところ、NOTCHやK-RASなどいくつかのがん遺伝子のmRNA量が低下していた。以上より、胃がんにおけるmiR-181cの発現低下にはメチル化が関与している可能性が考えられた。また、胃がんにおいてmiR-181cは細胞増殖やがん遺伝子の発現調節に関わるがん抑制的なmiRNAであると推測された。

  • Research Products

    (41 results)

All 2011 2010

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (33 results) Book (1 results)

  • [Journal Article] Epigenetics in molecular epidemiology of cancer : A new scope.2011

    • Author(s)
      Yuasa Y
    • Journal Title

      Adv.Genet.

      Volume: 71 Pages: 211-235

    • Peer Reviewed
  • [Journal Article] MicroRNA-126 Inhibits SOX2 Expression and Contributes to Gastric Carcinogenesis.2011

    • Author(s)
      Otsubo T, et al.
    • Journal Title

      PLoS One

      Volume: 6 Pages: 16617

    • Peer Reviewed
  • [Journal Article] MiR-9 down-regulates CDX2 expression in gastric cancer cells.2011

    • Author(s)
      Rotkrua P, et al.
    • Journal Title

      Int.J.Cancer

      Volume: in press

    • Peer Reviewed
  • [Journal Article] Loss of E-cadherin in mouse gastric epithelial cells induces signet ring-like cells, possible precursor lesion of diffuse gastric cancer.2011

    • Author(s)
      Mimata A, et al.
    • Journal Title

      Cancer Sci.

      Volume: in press

    • Peer Reviewed
  • [Journal Article] Human glioblastoma cells exposed to long-term hypoxia and nutrient starvation stimulated induction of secondary T cell leukemia in mice.2011

    • Author(s)
      Osawa T, et al.
    • Journal Title

      Blood Cancer Journal

      Volume: in press

    • Peer Reviewed
  • [Journal Article] miR-212 is down-regulated and suppresses methyl-CpG-binding protein MeCP2 inhuman gastric cancer.2010

    • Author(s)
      Wada R, et al.
    • Journal Title

      Int.J.Cancer

      Volume: 127 Pages: 1106-1114

    • Peer Reviewed
  • [Journal Article] Involvement of epigenetically silenced microRNA-181 c in gastric carcinogenesis.2010

    • Author(s)
      Hashimoto Y, et al.
    • Journal Title

      Carcinogenesis

      Volume: 31 Pages: 774-784

    • Peer Reviewed
  • [Presentation] Target gene analysis of GATA4 and GATA5 transcription factors in gastric cancer cells2011

    • Author(s)
      Akiyama Y, 他
    • Organizer
      The 10^<th> Japan-Korea Joint Symposium on Cancer and Ageing Research
    • Place of Presentation
      東京
    • Year and Date
      2011-02-15
  • [Presentation] MicroRNA-126 inhibits SOX2 expression in gastric cancers.2011

    • Author(s)
      Otsubo T, 他
    • Organizer
      The 10^<th> Japan-Korea Joint Symposium on Cancer and Ageing Research
    • Place of Presentation
      東京
    • Year and Date
      2011-02-15
  • [Presentation] MiR-9 down-regulates CDX2 expression in gastric carcinogenesis.2011

    • Author(s)
      Rotkrua R, 他
    • Organizer
      The 10^<th> Japan-Korea Joint Symposium on Cancer and Ageing Research
    • Place of Presentation
      東京
    • Year and Date
      2011-02-15
  • [Presentation] Up-regulation of multiple miRNA by treatment with chromatin-modifying drugs and identification of common target genes in gastric cancer cells.2011

    • Author(s)
      Hashimoto Y, 他
    • Organizer
      The 10^<th> Japan-Korea Joint Symposium on Cancer and Ageing Research
    • Place of Presentation
      東京
    • Year and Date
      2011-02-15
  • [Presentation] Synaergistic tumor suppressor activity of E-cadherin and p53 in a conditional mouse model for diffuse type gastric cancer2011

    • Author(s)
      Shimada S, 他
    • Organizer
      The 10^<th> Japan-Korea Joint Symposium on Cancer and Ageing Research
    • Place of Presentation
      東京
    • Year and Date
      2011-02-15
  • [Presentation] 胃がんとエピジェネティクス2010

    • Author(s)
      湯浅保仁、島田周、長崎弘美、三又絢子
    • Organizer
      第69回日本癌学会総会
    • Place of Presentation
      大阪
    • Year and Date
      20100922-20100924
  • [Presentation] Mouse model of diffuse-type gastric cancer by inactivating E-cadherin, which is involving in EMT and p53.2010

    • Author(s)
      Shimada S, 他
    • Organizer
      The 15th Korea-Japan Cancer Research Workshop
    • Place of Presentation
      Seoul, 韓国
    • Year and Date
      2010-12-22
  • [Presentation] MiR-9 down-regulates CDX2 expression in gastric cancer cells.2010

    • Author(s)
      Rotkrua P, 他
    • Organizer
      NSFC A3 Foresight Program 2010 Seminar
    • Place of Presentation
      Beijing, 中国
    • Year and Date
      2010-10-19
  • [Presentation] Loss of E-cadherin in parietal cells affects gastric epithelial cell polarity, growth and differentiation, resulting in a pre-malignant condition in mice.2010

    • Author(s)
      Mimata A, 他
    • Organizer
      NSFC A3 Foresight Program 2010 Seminar
    • Place of Presentation
      Beijing, 中国
    • Year and Date
      2010-10-19
  • [Presentation] Target gene analysis of GATA4 and GATA5 transcription factors in gastric cancer cells.2010

    • Author(s)
      Akiyama Y, 他
    • Organizer
      NSFC A3 Foresight Program 2010 Seminar
    • Place of Presentation
      Beijing, 中国
    • Year and Date
      2010-10-18
  • [Presentation] MicroRNA-126 inhibits SOX2 expression and consequent changes in expression of SOX2 target genes in gastric cancer cells.2010

    • Author(s)
      Otsubo T, 他
    • Organizer
      NSFC A3 Foresight Program 2010 Seminar
    • Place of Presentation
      Beijing, 中国
    • Year and Date
      2010-10-18
  • [Presentation] Effect of c-myc siRNA on the growth of gastric cancer cells.2010

    • Author(s)
      Hiratsuka A, 他
    • Organizer
      NSFC A3 Foresight Program 2010 Seminar
    • Place of Presentation
      Beijing, 中国
    • Year and Date
      2010-10-18
  • [Presentation] Up-regulation of several miRNAs by treatment with DNA demethylating agent and identification of common target genes in gastric cancer cells.2010

    • Author(s)
      Hashimoto Y, 他
    • Organizer
      NSFC A3 Foresight Program 2010 Seminar
    • Place of Presentation
      Beijing, 中国
    • Year and Date
      2010-10-18
  • [Presentation] Synergistic tumor suppressor activity of E-cadherin and p53 in a conditional mouse model for metastatic diffuse-type gastric cancer.2010

    • Author(s)
      Shimada S, 他
    • Organizer
      NSFC A3 Foresight Program 2010 Seminar
    • Place of Presentation
      Beijing, 中国
    • Year and Date
      2010-10-18
  • [Presentation] Identification of tumor-initiating cells in human gastric cancers.2010

    • Author(s)
      Fukamachi H, 他
    • Organizer
      NSFC A3 Foresight Program 2010 Seminar
    • Place of Presentation
      Beijing, 中国
    • Year and Date
      2010-10-18
  • [Presentation] Hypermethylation of GATA4 and GATA5 transcription factor genes and loss of their functions in gastric cancers.2010

    • Author(s)
      Akiyama Y, 他
    • Organizer
      The Second International Cancer Epigenetics Symposium
    • Place of Presentation
      Beijing, 中国
    • Year and Date
      2010-10-17
  • [Presentation] 胃がん細胞における転写因子GATA4とGATA.5転写因子の標的遺伝子の解析2010

    • Author(s)
      秋山好光, 他
    • Organizer
      第69回日本癌学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-24
  • [Presentation] miR-9のエピジェネティック変化は、 CDX2の発現異常を介して胃のがん化に関与する2010

    • Author(s)
      Rotkma P, 他
    • Organizer
      第69回日本癌学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-24
  • [Presentation] Identification of tumor-initiating cells in human gastric cancers.2010

    • Author(s)
      Fukamachi H, 他
    • Organizer
      第69回日本癌学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-24
  • [Presentation] マイクロRNA-126はSOX2発現を抑制し胃がん発症に関わる2010

    • Author(s)
      大坪武史, 他
    • Organizer
      第69回日本癌学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-23
  • [Presentation] Precancerous changes are induced in E-cadherin KO mouse stomachs.2010

    • Author(s)
      Mimata A, 他
    • Organizer
      第69回日本癌学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-23
  • [Presentation] びまん浸潤型胃癌動物モデルとしてのE-cadherinとp53のコンディショナルノックアウトマウス2010

    • Author(s)
      島田周, 他
    • Organizer
      第69回日本癌学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-22
  • [Presentation] 胃がんにおけるmiRNAクラスターの発現とメチル化の解析2010

    • Author(s)
      橋本裕, 他
    • Organizer
      第69回日本癌学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-22
  • [Presentation] Target gene analysis of GATA4/5 transcription factors in gastric cancers.2010

    • Author(s)
      Akiyama Y, 他
    • Organizer
      The 5th Asian Epigenomics Meeting & A3Symposium 2010
    • Place of Presentation
      Jeju Island, 韓国
    • Year and Date
      2010-06-21
  • [Presentation] Identification of tumor-initiating cells in human gastric cancers.2010

    • Author(s)
      Fukamachi H, 他
    • Organizer
      The 5th Asian Epigenomics Meeting & A3Symposium 2010
    • Place of Presentation
      Jeju Island, 韓国
    • Year and Date
      2010-06-21
  • [Presentation] Epigenetic epidemiology of gastric cancer.2010

    • Author(s)
      Yuasa Y, 他
    • Organizer
      The 5th Asian Epigenomics Meeting & A3Symposium 2010
    • Place of Presentation
      Jeju Island, 韓国
    • Year and Date
      2010-06-20
  • [Presentation] MicroRNA-126 inhibits SOX2 expression in gastric carcinogenesis.2010

    • Author(s)
      Otsubo T, 他
    • Organizer
      The 5th Asian Epigenomics Meeting & A3Symposium 2010
    • Place of Presentation
      Jeju Island, 韓国
    • Year and Date
      2010-06-20
  • [Presentation] Epigenetically repressed microRNA miR-181c targets oncogenic K-RAS and NOTCH4 in gastric cancer.2010

    • Author(s)
      Hashimoto Y, 他
    • Organizer
      The 5th Asian Epigenomics Meeting & A3Symposium 2010
    • Place of Presentation
      Jeju Island, 韓国
    • Year and Date
      2010-06-20
  • [Presentation] Epigenetic inactivation of the miR-9 genes in gastric carcinogenesis through CDX2 deregulation.2010

    • Author(s)
      Rotkrua P, 他
    • Organizer
      The 5th Asian Epigenomics Meeting & A3Symposium 2010
    • Place of Presentation
      Jeju Island, 韓国
    • Year and Date
      2010-06-20
  • [Presentation] Relationship between the methylation state of blood leukocyteDNA and carcinogenesis2010

    • Author(s)
      湯浅保仁, 他
    • Organizer
      第4回日本エピジェネティクス研究会年会
    • Place of Presentation
      鳥取
    • Year and Date
      2010-05-28
  • [Presentation] The target gene analyses of GATA4/5 transcription factors in gastric cancer.2010

    • Author(s)
      秋山好光, 他
    • Organizer
      第4回日本エピジェネティクス研究会年会
    • Place of Presentation
      鳥取
    • Year and Date
      2010-05-28
  • [Presentation] MicroRNA-126 inhibits SOX2 expression in gastric cancer cells.2010

    • Author(s)
      Otsubo T, 他
    • Organizer
      101^<st> AACR Annual Meeting
    • Place of Presentation
      Washington DC, 米国
    • Year and Date
      2010-04-19
  • [Presentation] Methylation of GATA4 and GATA5 transcription factor genes in gastric cancers.2010

    • Author(s)
      Akiyama Y, 他
    • Organizer
      101^<St> AACR Annual Meeting
    • Place of Presentation
      Washington DC, 米国
    • Year and Date
      2010-04-18
  • [Book] 分子予防環境医学2010

    • Author(s)
      湯浅保仁
    • Total Pages
      850
    • Publisher
      本の泉社

URL: 

Published: 2012-07-19  

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