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The effects of activation of canonical Wnt signaling on the proliferation and differentiation of gastric epithelial cells

Research Project

Project/Area Number 24790381
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Experimental pathology
Research InstitutionGifu University

Principal Investigator

HIRATA Akihiro  岐阜大学, 生命科学総合研究支援センター, 助教 (30397327)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords胃癌 / Wntシグナル / 細胞増殖 / 細胞分化 / 胃 / βカテニン / 胃上皮幹細胞 / β-カテニン / β-catenin / Wnt シグナル / 増殖 / 分化
Outline of Final Research Achievements

Wnt/β-catenin signaling is frequently activated in gastric cancers but it remains poorly understood how Wnt signaling contributes to the gastric carcinogenesis. In the present study, we investigated the effect of activation of Wnt signaling in gastric epithelial cells using doxycycline-inducible β-catenin mice. When we fed adult mice doxycycline for 5 days, cytoplasmic and nuclear β-catenin accumulation were observed in both fundic and pyloric glands of the stomach and the number of Ki-67-positive proliferating cells significantly increased in the isthmus and gastric pits with significant decrease in mucus production. Gene expression analysis revealed that β-catenin induction led to the up-regulations of gastric and intestinal epithelial stem cell markers. Our data indicate that Wnt activation maintains gastric epithelial cells in an undifferentiated and proliferative state.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (34 results)

All 2015 2014 2013 2012

All Journal Article (13 results) (of which Peer Reviewed: 13 results,  Open Access: 4 results) Presentation (21 results)

  • [Journal Article] Ectopic Tissue Consisting of a Mixture of Glandular Gastric, Intestinal, and Exocrine Pancreatic Tissue in the Forestomach of a Rat2014

    • Author(s)
      Kato Y, Hirata A, Kashiwagi E, Mauno K, Fujisawa K, Matsushima S, Takasu N.
    • Journal Title

      Journal of Toxicologic Pathology

      Volume: 27 Issue: 1 Pages: 87-90

    • DOI

      10.1293/tox.2013-0058

    • NAID

      130003391340

    • ISSN
      0914-9198, 1881-915X
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Choriocarcinoma-like tumor in a potbellied pig (Sus scrofa)2014

    • Author(s)
      Hirata A*, Miyazaki A, Sakai H, Imada N, Kitani R, Nikami H and Yanai T
    • Journal Title

      Journal of Veterinary Diagnostic Investigation

      Volume: 26 Issue: 1 Pages: 163-166

    • DOI

      10.1177/1040638713515481

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Time-sensitive effects of hypoxia on differentiation of neural stem cells derived from mouse embryonic stem cells in vitro.2014

    • Author(s)
      Binh NH, Aoki H, Takamatsu M, Hatano Y, Hirata A, Tomita H, and Hara A.
    • Journal Title

      Neurol. Res.

      Volume: 36 Issue: 9 Pages: 804-813

    • DOI

      10.1179/1743132814y.0000000338

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunocytochemical detection of the class A macrophage scavenger receptor CD204 in air-dried cytological smears of canine histiocytic sarcoma.2014

    • Author(s)
      Kato, Y, Funato R, Hirata A, Murakami M, Mori T, Maruo K, Yanai T, Sakai, H.
    • Journal Title

      Vet. Clin. Pathol.

      Volume: 43 Issue: 4 Pages: 589-593

    • DOI

      10.1111/vcp.12190

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The class A macrophage scavenger receptor CD204 is a useful immunohistochemical marker of canine histiocytic sarcoma.2013

    • Author(s)
      Kato Y, Murakami M, Hoshino Y, Mori T, Maruo K, Hirata A, Nakagawa TL, Yanai
    • Journal Title

      J Comp Pathol

      Volume: 148 Issue: 2-3 Pages: 188-196

    • DOI

      10.1016/j.jcpa.2012.06.009

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Combined effects of organochlorine pesticides heptachlor and hexachlorobenzene on the promotion stage of hepatocarcinogenesis in rat2013

    • Author(s)
      Abdo W, Hirata A*, Sakai H, Ahmed ES, Nikami H, Yanai T
    • Journal Title

      Food and Chemical Toxicology

      Volume: 55 Pages: 578-585

    • DOI

      10.1016/j.fct.2013.01.035

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] IDO1 plays an immunosuppressive role in 2, 4, 6-trinitrobenzene sulfate-induced colitis in mice2013

    • Author(s)
      Takamatsu M, Hirata A, Ohtaki H, Hoshi M, Hatano Y, Tomita H, Kuno T, Saito K, Hara A
    • Journal Title

      J Immunol

      Volume: 15;191(6) Issue: 6 Pages: 3057-64

    • DOI

      10.4049/jimmunol.1203306

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dose-dependent roles for canonical Wnt signaling in de novocrypt formation and cell cycle properties of the colonic epithelium.2013

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

      Development.

      Volume: 140(1) Issue: 1 Pages: 66-75

    • DOI

      10.1242/dev.084103

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Organomagnesium suppresses inflammation-associated colon carcinogenesis in male Crj: CD-1 mice.2013

    • Author(s)
      Kuno, T., Hatano, Y., Tomita, H., Hara, A., Hirose, Y., Hirata, A., Mori, H., Terasaki, M, Masuda, S., and Tanaka, T.
    • Journal Title

      Carcinogenesis

      Volume: 34 Issue: 2 Pages: 361-369

    • DOI

      10.1093/carcin/bgs348

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Galectin-3 in preneoplastic lesions of glioma.2013

    • Author(s)
      Bihn NH, Satoh K, Kobayashi K, Takamatsu M, Hatano Y, Hirata A, Tomita H, Kuno T and Hara A.
    • Journal Title

      Journal of Neuro-Oncology

      Volume: 111 Issue: 2 Pages: 123-132

    • DOI

      10.1007/s11060-012-1005-2

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Spontaneous T/NK-cell lymphoma associated with Simian Lymphocryptovirus in a Japanese Macaque (Macaca fuscata).2013

    • Author(s)
      Hirata A, Tachikawa Y, Hashimoto K, Sakai H, Kaneko A, Suzuki J, Eguchi K, Shigematsu K, Nikami H, and Yanai T.
    • Journal Title

      Journal of Comparative Pathology

      Volume: 148 Issue: 1 Pages: 43-48

    • DOI

      10.1016/j.jcpa.2012.05.001

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Constitutive phosphorylation of the mTORC2/Akt/4E-BP 1 pathway in newly derived canine hemangiosarcoma cell lines2012

    • Author(s)
      Murai, A., Asa, SA., Kodama , A., Hirata, A., Yanai, T. and Sakai, H.
    • Journal Title

      BMC Veterinary Research

      Volume: 8 Issue: 1 Pages: 128-128

    • DOI

      10.1186/1746-6148-8-128

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Immunohistochemical analysis of the Akt/mTOR/4E-BP 1 signalling pathway in canine haemangiomas and haemangiosarcomas2012

    • Author(s)
      Murai, A., Asa, SA., Kodama, A., Sakai, H., Hirata, A. and Yanai , T.
    • Journal Title

      Journal of Comparative Pathology

      Volume: 147 Issue: 4 Pages: 430-440

    • DOI

      10.1016/j.jcpa.2012.05.002

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Wntシグナル活性化による胃上皮細胞の分化・増殖制御機構の破綻:胃癌の発生・進展機構の解析2015

    • Author(s)
      平田 暁大、山田 泰広、富田 弘之、塚本 徹哉、原 明
    • Organizer
      第31回日本毒性病理学会
    • Place of Presentation
      東京
    • Year and Date
      2015-01-29 – 2015-01-30
    • Related Report
      2014 Annual Research Report
  • [Presentation] 大腸粘膜修復過程で生じる再生陰窩における大腸上皮幹細胞、増殖細胞、分化細胞の動態2015

    • Author(s)
      村井 厚子、平田 暁大、柳井 徳磨、原 明
    • Organizer
      第31回日本毒性病理学会
    • Place of Presentation
      東京
    • Year and Date
      2015-01-29 – 2015-01-30
    • Related Report
      2014 Annual Research Report
  • [Presentation] マウス胃上皮細胞におけるβ-カテニン強制発現による遺伝子発現変化の解析2014

    • Author(s)
      平田 暁大、山田 泰広、富田 弘之、波多野裕一郎、原 明
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 玄米酵素食によるBOP誘発ハムスター膵発癌の抑制効果2014

    • Author(s)
      久野 壽也、森 秀樹、内木-伊藤 綾、田中 卓二、久松 憲治、富田 弘之、原 明、平田 暁大、高橋 智
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] ApcMin/+マウスの大腸腫瘍性病変における腸管上皮幹細胞マーカーLgr5発現細胞の機能解析2014

    • Author(s)
      平田 暁大、久野 壽也、高松 学、波多野 裕一郎、富田 弘之、原 明
    • Organizer
      第30回日本不毒性病理学会
    • Place of Presentation
      徳島
    • Related Report
      2013 Research-status Report
  • [Presentation] EHEN投与ラットの前腸由来臓器への分化多能性を示す肝芽腫の一例2014

    • Author(s)
      山野荘太郎、尾崎清和、武田周二、串田昌彦、井澤武史、山手丈至、平田暁大、藤岡正喜、魏民、鰐淵英機
    • Organizer
      第30回日本不毒性病理学会
    • Place of Presentation
      徳島
    • Related Report
      2013 Research-status Report
  • [Presentation] ApcMin/+マウスの大腸腫瘍性病変における腸管上皮幹細胞マーカーLgr5発現細胞の役割2013

    • Author(s)
      平田 暁大、久野 壽也、高松 学、波多野 裕一郎、富田 弘之、原 明
    • Organizer
      第20回がん予防学会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] 炎症関連TSODマウス大腸発癌に対するACE阻害剤enalaprilの修飾効果2013

    • Author(s)
      久野 壽也、田中 卓二、三輪 貴生、小川 博史、遠藤 奨、後藤 滉平、平田 暁大、廣瀬 善信、原 明
    • Organizer
      第20回がん予防学会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] ApcMin/+マウスの大腸腫瘍性病変におけるLgr5発現細胞の機能解析2013

    • Author(s)
      平田 暁大、高松 学、富田 弘之、波多野 裕一郎、久野 壽也、原 明
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] Indoleamine-2,3-dioxygenase (IDO) 欠損の大腸腫瘍に与える影響2013

    • Author(s)
      高松 学、平田 暁大、波多野 裕一郎、富田 弘之、久野 壽也、原 明
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] デオキシコール酸はAOM誘発マウス大腸腫瘍を近位ではなく遠位大腸において促進する2013

    • Author(s)
      久野 壽也、田中 卓二、富田 弘之、廣瀬 善信、平田 暁大、原 明
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] Wntシグナルによる胃上皮細胞および胃癌細胞の分化・増殖制御2013

    • Author(s)
      平田 暁大、山田 泰広、富田 弘之、塚本 徹哉、山本 昌美、二上 英樹、原 明
    • Organizer
      第156回日本獣医学会学術集会
    • Place of Presentation
      岐阜
    • Related Report
      2013 Research-status Report
  • [Presentation] ニホンザルの心臓の線維化に関する病理組織学的所見2013

    • Author(s)
      加藤 由隆、平田 暁大、兼子明久、鈴木樹理、酒井 洋樹、柳井 徳磨
    • Organizer
      第156回日本獣医学会学術集会
    • Place of Presentation
      岐阜
    • Related Report
      2013 Research-status Report
  • [Presentation] Wntシグナルによる胃上皮細胞および胃癌細胞の分化・増殖制御に関する研究2013

    • Author(s)
      平田 暁大、山田 泰広、富田 弘之、久野 壽也、村井 厚子、塚本 徹哉、山本 昌美、原 明
    • Organizer
      第29回日本毒性病理学会
    • Place of Presentation
      筑波
    • Related Report
      2012 Research-status Report
  • [Presentation] Dextran sulfate sodium (DSS) 誘発性大腸炎の粘膜修復過程における腸管上皮幹細胞の役割2013

    • Author(s)
      村井 厚子、平田 暁大、高松 学、久野 壽也、柳井 徳磨、原 明
    • Organizer
      第29回日本毒性病理学会
    • Place of Presentation
      筑波
    • Related Report
      2012 Research-status Report
  • [Presentation] マウス炎症性大腸発がんにおけるDNAメチル化の意義2012

    • Author(s)
      波多野裕一郎、橋本恭一、平田 暁大、富田 弘之、久野 壽也、高松 学、山下 聡、武藤 誠、原 明、牛島 俊和、山田 泰広
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] Wntシグナルによるマウス胃上皮細胞および胃癌細胞の増殖・分化制御2012

    • Author(s)
      平田 暁大、山田 泰広、富田 弘之、高松 学、波多野 裕一郎、久野 壽也、村井 厚子、塚本 徹哉、原 明
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] Indoleamine-2,3-dioxygenase (IDO) 欠損による2,4,6-Trinitrobenzene sulfate (TNBS) 誘発性大腸炎促進効果2012

    • Author(s)
      高松 学、平田 暁大、波多野 裕一郎、久野 壽也、原 明
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] 肥満・高脂血症モデルマウスにおけるPPARαアゴニスト、フェノフィブラートの4-NQO誘発肺増殖性病変抑制効果の検討2012

    • Author(s)
      久野 壽也、田中 卓二、高松 学、波多野 裕一郎、富田 弘之、廣瀬 善信、平田 暁大、原 明
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] 犬組織球肉腫におけるMatrix metallopproteinase (MMP) の免疫組織学的検索2012

    • Author(s)
      船戸 里沙、米丸 加余子、村上 麻美、森 崇、丸尾 幸嗣、平田 暁大、柳井 徳磨、酒井 洋樹
    • Organizer
      第154回日本獣医学会学術集会
    • Place of Presentation
      岩手
    • Related Report
      2012 Research-status Report
  • [Presentation] Dose-dependent roles for canonical Wnt signaling in de novo crypt formation and cell cycle properties of colonic epithelium.2012

    • Author(s)
      Hirata A, Utikal J, Yamashita S, Aoki H, Watanabe A, Yamamoto T, Okano H, Bardeesy N, Kunisada T, Ushijima T, Hara A, Jaenisch R, Hochedlinger K and Yamada Y
    • Organizer
      International Society for Stem Cell Research 10th Annual Meeting
    • Place of Presentation
      Yokohama
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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