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2012 Fiscal Year Final Research Report

Development of YAP-dependent hepatic tumor formation and analysis of global expression of related microRNAs

Research Project

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Project/Area Number 24659030
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Biological pharmacy
Research InstitutionTokyo Medical and Dental University

Principal Investigator

NISHINA Hiroshi  東京医科歯科大学, 難治疾患研究所, 教授 (60212122)

Project Period (FY) 2012
KeywordsYAP / 肝癌 / 細胞競合 / アポトーシス / cDNA / マイクロRNA / HTVi法 / 網羅的遺伝子解析
Research Abstract

Recently, YAP was shown to play an important role in organ size control and to be inhibited by the Hippo signaling pathway. Either transgenic overexpression of YAP or knockout of Hippo pathway genes in mouse liver results in enlargement of this organ and the eventual development of hepatic tumors. In this study, we used the method of hydrodynamic tail vein injection (HTVi) that is specific for gene transfer into liver. As a results, we succeeded in establishing an efficient system of liver cancer induction due to gain of function of the active YAP. Secondly, we analyzed the gene expression by cDNA microarray and identified more than 20 genes whose expression is increased by active YAP. Thus, our results could contribute to elucidate the mechanismof human liver cancer.

  • Research Products

    (46 results)

All 2012 Other

All Journal Article (14 results) Presentation (31 results) Remarks (1 results)

  • [Journal Article] A novel acetylation cycle of the transcription co-activator Yes-associated protein that is downstream of the Hippo pathway is triggered in response to SN2 alkylating agents2012

    • Author(s)
      Shoji Hata, Jun Hirayama, Hiroaki Kajiho, Kentaro Nakagawa, Yutaka Hata, Toshiaki Katada, Makoto Furutani-Seiki and Hiroshi Nishina
    • Journal Title

      J. Biol. Chem

      Volume: 287 Pages: 22089-22098

  • [Journal Article] Involvement of the Stress Kinase Mitogen-activated Protein Kinase Kinase 7 in the Regulation of the Mammalian Circadian Clock2012

    • Author(s)
      Yoshimi Uchida, Tomomi Osaki, Tokiwa Yamasaki, Tadanori Shimomura, Shoji Hata, Kazumasa Horikawa, Shigenobu Shibata, Takeshi Todo, Jun Hirayama and Hiroshi Nishina
    • Journal Title

      J. Biol. Chem

      Volume: 287 Pages: 8318-8326

  • [Journal Article] Light, reactive oxygen species, and magnetic fields activate ERK/MAPK signaling pathway in cultured zebrafish cells2012

    • Author(s)
      Yoshimi Uchida, Tadanori Shimomura, Jun Hirayama and Hiroshi Nishina
    • Journal Title

      Appl. Magn.Reson

      Volume: 42 Pages: 69-77

  • [Journal Article] Cancer Susceptibility andembryonic lethality in Mob1A/1Bdouble mutant mice2012

    • Author(s)
      Miki Nishio, Koichi Hamada, Kohichi Kawahara, Masato Sasaki, Fumihito Noguchi, Shuhei Chiba, Kensaku Mizuno, Satoshi O. Suzuki, Youyi Dong, Masaaki Tokuda, Takumi Morikawa, Hiroki Hikasa, Jonathan Eggenschwiler, Norikazu Yabuta, Hiroshi Nojima, Kentaro Nakagawa, Yutaka Hata, Hiroshi Nishina, Koshi Mimori, Masaki Mori, Takehiko Sasaki, Tak W. Mak, Toru Nakano, Satoshi Itami, and Akira Suzuki
    • Journal Title

      J. Clin. Invest

      Volume: 122(12) Pages: 4505-4518

  • [Journal Article] Establishment of Functioning Human Corneal Endothelial Cell Line with High Growth Potential2012

    • Author(s)
      Tadashi Yokoi, Yuko Seko, Tae Yokoi, Hatsune Makino, Shin Hatou, Masakazu Yamada, Tohru Kiyono, Akihiro Umezawa, Hiroshi Nishina, Noriyuki Azuma
    • Journal Title

      PLoS ONE

      Volume: 7(1) Pages: e29677

  • [Journal Article] Prospective isolation and characterization of bipotent progenitor cells in early mouse liver development2012

    • Author(s)
      Ken Okada, Akihide Kamiya,Keiichi Ito, Ayaka Yanagida, Hidenori Ito, Hiroki Kondou, Hiroshi Nishina and Hiromitsu Nakauchi
    • Journal Title

      Stem Cells and Development

      Volume: 21 Pages: 1124-1133

  • [Journal Article] Splenectomy enhances the anti-fibrotic effect of bone marrow cell infusion and improves liver function in cirrhotic mice and patients2012

    • Author(s)
      Takuya Iwamoto, Shuji Terai, Yuko Mizunaga, Naoki Yamamoto, Kaoru Omori, Koichi Uchida, Takahiro Yamasaki, Yasuhiko Fujii, Hiroshi Nishina, and Isao Sakaida
    • Journal Title

      J. Gastroenterol

      Volume: 47 Pages: 300-312

  • [Journal Article] Ezetimibe reduces fatty acid quantity in liver and decreased inflammatory cell infiltration and improved NASH in medaka model2012

    • Author(s)
      Toshiyuki Oishi, Shuji Terai, Shinya Kuwashiro, Koichi Fujisawa, Toshihiko Matsumoto, Hiroshi Nishina and Isao Sakaida
    • Journal Title

      Biochem. Biophys. Res. Commun

      Volume: 422 Pages: 22-27

  • [Journal Article] [Letters to the Editor] Reply to Sun et al.: Targeting YAP acetylation in cancer2012

    • Author(s)
      Shoji Hata and Hiroshi Nishina
    • Journal Title

      J. Biol. Chem

      Volume: 287 Pages: 35443

  • [Journal Article] Diverse roles of JNK and MKK pathways in the brain2012

    • Author(s)
      Tokiwa Yamasaki, Hiroshi Kawasaki and Hiroshi Nishina
    • Journal Title

      J. Signal Trans

      Pages: 459265

  • [Journal Article] [commentary] hDlk-1: A cell surface marker common to normal hepatic stem/progenitor cells and carcinomas2012

    • Author(s)
      Hiroshi Nishina
    • Journal Title

      J. Biochem

      Volume: 152 Pages: 121-123

  • [Journal Article] 活性酸素シグナルと概日リズム2012

    • Author(s)
      平山順、仁科博史
    • Journal Title

      実験医学2012年11月増刊号

      Pages: 36-41

  • [Journal Article] モデル生物を用いた肝発生および肝サイズ制御機構の解明2012

    • Author(s)
      宮村憲央、仁科博史
    • Journal Title

      肝胆膵

      Volume: 65 Pages: 21-28

  • [Journal Article] 質量顕微鏡法を用いたマウス再生肝の解析2012

    • Author(s)
      宮村憲央、瀬藤光利、仁科博史
    • Journal Title

      生化学

      Volume: 84 Pages: 680-684

  • [Presentation] 器官サイズ制御因子YAPの網膜分化における機能解析2012

    • Author(s)
      浅岡洋一
    • Organizer
      第5回RRM
    • Place of Presentation
      東京
    • Year and Date
      20121200
  • [Presentation] がん遺伝子yap依存的異常肝細胞の排除と肝細胞がんの発症2012

    • Author(s)
      仁科博史
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Year and Date
      20121200
  • [Presentation] ストレス応答性キナーゼによる概日リズム制御2012

    • Author(s)
      平山順他
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Year and Date
      20121200
  • [Presentation] がん遺伝子産物YAPアセチル化サイクルの同定2012

    • Author(s)
      畠星治他
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡
    • Year and Date
      20121200
  • [Presentation] A novel acetylation cycle of the transcription co-activator Yes-associated protein that is downstream of the Hippo pathway is triggered in response to SN2alkylating agents2012

    • Author(s)
      Shoji Hata and Hiroshi Nishina
    • Organizer
      InternationalSymposium on GENETIC AND EPIGENETIC CONTROL OF CELL FATE
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      20121100
  • [Presentation] Liver Formation and Disease: Lessons from Fish and Mouse2012

    • Author(s)
      Hiroshi Nishina
    • Organizer
      4th World Congress of Pediatric Gastroentrology, Hepatology and Nutrition
    • Place of Presentation
      Taipei, Taiwan
    • Year and Date
      20121100
  • [Presentation] Stress-activated protein kinase MKK7 regulatesaxon elongation in the developing cerebral cortex2012

    • Author(s)
      Tokiwa Yamasaki
    • Organizer
      Neuroscience 2012, SfN's 42nd annual meeting
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      20121000
  • [Presentation] がん遺伝子YAPによる肝細胞癌発症機構の解明2012

    • Author(s)
      宮村憲央
    • Organizer
      第17回日本肝臓医生物学研究会
    • Place of Presentation
      旭川
    • Year and Date
      20121000
  • [Presentation] がん遺伝子YAP誘導性肝細胞がんのゲノム解析2012

    • Author(s)
      千葉恭敬
    • Organizer
      第17回日本肝臓医生物学研究会
    • Place of Presentation
      旭川
    • Year and Date
      20121000
  • [Presentation] YAPパラログTAZの肝がん誘導能の検討2012

    • Author(s)
      斎藤光介
    • Organizer
      第17回日本肝臓医生物学研究会
    • Place of Presentation
      旭川
    • Year and Date
      20121000
  • [Presentation] 神経細胞特異的欠損マウスを用いた概日リズム制御機構におけるストレス応答性キナーゼMKK7の機能解析2012

    • Author(s)
      有馬誉恵他
    • Organizer
      第11回次世代を担う若手ファーマ・バイオフォーラム
    • Place of Presentation
      福岡
    • Year and Date
      20120900
  • [Presentation] ストレス応答性MKK7-JNKシグナル経路による分子時計制御2012

    • Author(s)
      内田好海他
    • Organizer
      第11回ファーマバイオフォーラム2012
    • Place of Presentation
      福岡
    • Year and Date
      20120900
  • [Presentation] ストレス応答性リン酸化酵素による概日リズム制御2012

    • Author(s)
      平山順他
    • Organizer
      第19回日本時間生物学会学術大会
    • Place of Presentation
      札幌
    • Year and Date
      20120900
  • [Presentation] JNK signaling is required for the maintenance of motor performance in old-age animals2012

    • Author(s)
      山崎世和他
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋
    • Year and Date
      20120900
  • [Presentation] Light-dependentUV-tolerance in zebrafish early embryo2012

    • Author(s)
      平山順他
    • Organizer
      第18回小型魚類研究会
    • Place of Presentation
      京都
    • Year and Date
      20120900
  • [Presentation] Analysis of the Hippo signaling pathway regulating neuronal differentiation in the retina2012

    • Author(s)
      浅岡洋一他
    • Organizer
      第18回小型魚類研究会
    • Place of Presentation
      京都
    • Year and Date
      20120900
  • [Presentation] マウスとメダカから学ぶ肝形成と肝疾患2012

    • Author(s)
      仁科博史
    • Organizer
      秋田大学医学部セミナー
    • Place of Presentation
      秋田
    • Year and Date
      20120800
  • [Presentation] A novel acetylation cycle of the transcription co-activator Yes-associated protein that is downstream of the Hippo pathway is triggered in response to SN2 alkylatingagents2012

    • Author(s)
      Hiroshi Nishina
    • Organizer
      2012 FASEB Science ResearchConference
    • Place of Presentation
      Aspen, USA
    • Year and Date
      20120700
  • [Presentation] ストレス応答性MAPキナーゼシグナル伝達系のゼブラフィッシュ初期胚における役割の解明2012

    • Author(s)
      浅岡洋一
    • Organizer
      第34回日本比較生理生化学会,第21回吉田奨励賞受賞講演
    • Place of Presentation
      葉山
    • Year and Date
      20120700
  • [Presentation] 細胞の生死を制御するストレス応答性MKK7の神経系における生理的役割の解明2012

    • Author(s)
      山崎世和他
    • Organizer
      第21回日本Cell Death学会
    • Place of Presentation
      名古屋
    • Year and Date
      20120700
  • [Presentation] 質量顕微鏡法2012

    • Author(s)
      仁科博史
    • Organizer
      第55回日本腎臓学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      20120600
  • [Presentation] がん遺伝子産物YAPの新規翻訳後修飾アセチル化の同定2012

    • Author(s)
      畠星治他
    • Organizer
      第19回肝細胞研究会
    • Place of Presentation
      札幌
    • Year and Date
      20120600
  • [Presentation] がん遺伝子産物YAPによる細胞競合および肝がん誘導系の確立2012

    • Author(s)
      宮村憲央他
    • Organizer
      第19回肝細胞研究会
    • Place of Presentation
      札幌
    • Year and Date
      20120600
  • [Presentation] ストレス応答性キナーゼMKK7による概日リズム制御機構の解明2012

    • Author(s)
      内田好海他
    • Organizer
      第11回生命科学研究会
    • Place of Presentation
      秋田
    • Year and Date
      20120600
  • [Presentation] Analyses of physiological functions of stress kinase MKK7 in developing cortex and adult nervous system2012

    • Author(s)
      Tokiwa Yamasaki
    • Organizer
      Yale CNNR seminar
    • Place of Presentation
      New Haven, USA
    • Year and Date
      20120400
  • [Presentation] 神経組織特異的Mkk7欠損マウスの解析2012

    • Author(s)
      岩月麻美子他
    • Organizer
      第132回日本薬学会
    • Place of Presentation
      札幌
    • Year and Date
      20120300
  • [Presentation] がん遺伝子産物YAPの新規翻訳後修飾アセチル化の同定2012

    • Author(s)
      畠星治
    • Organizer
      第16回日本肝臓医生物学研究会
    • Place of Presentation
      熱海
    • Year and Date
      20120300
  • [Presentation] がん遺伝子YAPによる肝細胞がんの発症機構の解明2012

    • Author(s)
      宮村憲央
    • Organizer
      第16回日本肝臓医生物学研究会
    • Place of Presentation
      熱海
    • Year and Date
      20120300
  • [Presentation] Liver development , regeneration and disease: lessons from mice and fish2012

    • Author(s)
      仁科博史
    • Organizer
      第9回心血管幹細胞研究会
    • Place of Presentation
      東京
    • Year and Date
      20120100
  • [Presentation] Liver development , regeneration and disease: lessons from mice and fish2012

    • Author(s)
      仁科博史
    • Organizer
      東京大学薬学セミナー
    • Place of Presentation
      東京
    • Year and Date
      20120100
  • [Presentation] モデル生物を用いた器官形成機構の解明2012

    • Author(s)
      仁科博史
    • Organizer
      山口大学医学部セミナー
    • Place of Presentation
      宇部
    • Year and Date
      20120100
  • [Remarks]

    • URL

      http://www.tmd.ac.jp/mri/dbio/index.html

URL: 

Published: 2014-09-25  

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