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Functional analysis of PHLDA3, a tumor suppressor gene of neuroendocrine tumors

Research Project

Project/Area Number 26430133
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor biology
Research InstitutionNational Cancer Center Japan

Principal Investigator

Ohki Rieko  国立研究開発法人国立がん研究センター, 研究所, 主任研究員 (70356252)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords神経内分泌腫瘍 / PHLDA3 / p53 / Akt
Outline of Final Research Achievements

The purpose of this study is to clarify the mechanism of neuroendocrine tumor (NET) onset and to obtain results useful for NET treatment / diagnosis. We previosly found that the PHLDA3 gene encodes a novel Akt repressor and has been shown to function as a tumor suppressor gene in NET of lung and pancreas (Cell, Vol. 136 , p. 535-550, 2009, and PNAS, 111 (23), E2404-E2413, 2014). We believe that PHLDA 3 is a tumor suppressor gene of NET derived from various tissues, and we believe that Akt suppression by PHLDA3 plays a central role in NET suppression. Therefore, we believe that inhibitors of the Akt pathway may be effective for patients with LOH of the PHLDA3 gene. Furthermore, LOH of the PHLDA3 gene has a strong correlation with the prognosis of NET patients, and it is possible that LOH diagnosis of the PHLDA3 gene will make it possible to predict patient prognosis. By this research, we believe that we contributed to individualized medical care of NET patients.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (24 results)

All 2017 2016 2015 2014

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 7 results,  Acknowledgement Compliant: 3 results) Presentation (14 results) (of which Int'l Joint Research: 2 results,  Invited: 7 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] A vicious partnership between AKT and PHLDA3 to facilitate neuroendocrine tumors2017

    • Author(s)
      Masahiro Takikawa and Rieko Ohki
    • Journal Title

      Cancer Science

      Volume: 印刷中 Issue: 6 Pages: 1101-1108

    • DOI

      10.1111/cas.13235

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A novel p53 target gene FUCA1 encodes a fucosidase and regulates growth and survival of cancer cells.2016

    • Author(s)
      Ezawa I, Sawai Y, Kawase T, Okabe A, Tsutsumi S, Ichikawa H, Kobayashi Y, Tashiro F, Namiki H, Kondo T, Semba K, Aburatani H, Taya Y, Nakagama H, Ohki R.
    • Journal Title

      Cancer Sci.

      Volume: 印刷中 Issue: 6 Pages: 734-745

    • DOI

      10.1111/cas.12933

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] IER5 generates a novel hypo-phosphorylated active form of HSF1 and contributes to tumorigenesis.2016

    • Author(s)
      Yoshinori Asano, Tatsuya Kawase, Atsushi Okabe, Shuichi Tsutsumi, Hitoshi Ichikawa, Satoko Tatebe, Issay Kitabayashi, Fumio Tashiro, Hideo Namiki, Tadashi Kondo, Kentaro Semba, Hiroyuki Aburatani, Yoichi Taya, Hitoshi Nakagama and Rieko Ohki
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 19174-19174

    • DOI

      10.1038/srep19174

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] PHLDA2 is a key oncogene-induced negative feedback inhibitor of EGFR/ErbB2 signaling via interference with AKT signaling.2015

    • Author(s)
      Xiaoqi Wang, Guangyuan Li, Sanjay Koul, Rieko Ohki, Matthew Maurer, Alain Borczuk, Balazs Halmos.
    • Journal Title

      Oncotarget

      Volume: 10 Issue: 38 Pages: 18632-18632

    • DOI

      10.18632/oncotarget.3674

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 膵神経内分泌腫瘍の新規がん抑制遺伝子PHLDA3の発見2015

    • Author(s)
      陳 ヨ, 斉藤 梢, 山口 陽子, 大木 理恵子
    • Journal Title

      胆と膵

      Volume: 36 Pages: 515-523

    • Related Report
      2015 Research-status Report
  • [Journal Article] Identification of Non-Coding RNAs Associated with Telomeres Using a Combination of enChIP and RNA Sequencing2015

    • Author(s)
      Toshitsugu Fujita, Miyuki Yuno, Daisuke Okuzaki, Rieko Ohki, Hodaka Fujii
    • Journal Title

      PLOS ONE

      Volume: 10 Issue: 4 Pages: e0123387-e0123387

    • DOI

      10.1371/journal.pone.0123387

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] PHLDA2 is a key oncogene-induced negative feedback inhibitor of EGFR/ErbB2 signaling via interference with AKT signaling2015

    • Author(s)
      Xiaoqi Wang, Guangyuan Li, Sanjay Koul, Rieko Ohki, Matthew Maurer, Alain Borczuk, Balazs Halmos.
    • Journal Title

      Oncotarget

      Volume: なし

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] PHLDA3 is a novel tumor suppressor of pancreatic neuroendocrine tumors.2014

    • Author(s)
      Ohki R, Saito K, Chen Y, Kawase T, Hiraoka N, Saigawa R, Minegishi M, Aita Y, Yanai G, Shimizu H, Yachida S, Sakata N, Doi R, Kosuge T, Shimada K, Tycko B,Tsukada T, Kanai Y, Sumi S, Namiki H, Taya Y, Shibata T, Nakagama H.
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: Jun 10;111(23) Issue: 23

    • DOI

      10.1073/pnas.1319962111

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] がん抑制遺伝子PHLDA3の下垂体腺腫における機能喪失性変異の同定と機能解析2017

    • Author(s)
      山口 陽子、冨永 航平、陳 妤、峯岸 舞子、山田正三、大木理恵子
    • Organizer
      第27回日本間脳下垂体腫瘍学会
    • Place of Presentation
      日経カンファレンスルーム
    • Year and Date
      2017-02-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] PHLDA3は下垂体腺腫の新規がん抑制遺伝子である2017

    • Author(s)
      陳 妤、峯岸 舞子、斎藤 梢、山田正三、並木 秀男、仙波 憲太郎、大木理恵子
    • Organizer
      第27回日本間脳下垂体腫瘍学会
    • Place of Presentation
      日経カンファレンスルーム
    • Year and Date
      2017-02-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] 8.PH domain-only protein PHLDA3 is a novel p53-regulated repressor of Akt and a novel tumor suppressor of neuroendocrine tumors2016

    • Author(s)
      大木理恵子
    • Organizer
      日本分子生物学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-12-02
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] IER5 generates a novel hypo-phosphorylated active form of HSF1 and contributes to tumorigenesis2016

    • Author(s)
      大木 理恵子
    • Organizer
      Tenth AACR-JCA Joint Conference
    • Place of Presentation
      アメリカ ハワイ
    • Year and Date
      2016-02-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Aktの新規抑制因子をコードするPHLDA3遺伝子は 神経内分泌腫瘍のがん抑制遺伝子である2015

    • Author(s)
      大木 理恵子
    • Organizer
      日本分子生物学会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-04
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] PHLDA3遺伝子は下垂体神経内分泌腫瘍の新規がん抑制遺伝子である2015

    • Author(s)
      峯岸舞子、齋藤梢、チンヨ、會田雪絵、川瀬竜也、山田正三、並木秀男、仙波憲太郎、大木理恵子
    • Organizer
      日本分子生物学会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-03
    • Related Report
      2015 Research-status Report
  • [Presentation] p53標的遺伝子PAD5は、新規HSF1活性化因子をコードし、がん細胞生存に必須な遺伝子である2015

    • Author(s)
      大木 理恵子
    • Organizer
      日本癌学会年会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] PH domain-only protein PHLDA3 is a novel p53-regulated repressor of Akt and a novel tumor suppressor of neuroendocrine tumors2015

    • Author(s)
      大木理恵子
    • Organizer
      2015 SNUCRI Cancer Symposium
    • Place of Presentation
      韓国広州
    • Year and Date
      2015-04-03
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] PH domain-only protein PHLDA3 is a novel p53-regulated repressor of Akt and a novel tumor suppressor of neuroendocrine tumors2015

    • Author(s)
      大木 理恵子
    • Organizer
      SNUCRI Cancer Symposium
    • Place of Presentation
      韓国 広州
    • Year and Date
      2015-04-02
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] PH domain-only protein PHLDA3 is a novel p53-regulated repressor of Akt and a novel tumor suppressor of neuroendocrine tumors2014

    • Author(s)
      大木理恵子
    • Organizer
      日韓がんワークショップ
    • Place of Presentation
      韓国済州島
    • Year and Date
      2014-11-29
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] PH domain-only protein PHLDA3 is a novel p53-regulated repressor of Akt and a novel tumor suppressor of neuroendocrine tumors2014

    • Author(s)
      大木理恵子
    • Organizer
      日独がんワークショップ
    • Place of Presentation
      ドイツベルリン
    • Year and Date
      2014-11-15
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] PH domain-only protein PHLDA3 is a novel p53-regulated repressor of Akt and a novel tumor suppressor of neuroendocrine tumors2014

    • Author(s)
      大木理恵子
    • Organizer
      日本癌学会年会
    • Place of Presentation
      神奈川県横浜市
    • Year and Date
      2014-09-27
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Aktの新規抑制因子をコードするPHLDA3遺伝子は神経内分泌腫瘍のがん抑制遺伝子である2014

    • Author(s)
      大木理恵子
    • Organizer
      第2回日本神経内分泌腫瘍研究会学術集会
    • Place of Presentation
      東京都文京区
    • Year and Date
      2014-09-20
    • Related Report
      2014 Research-status Report
  • [Presentation] PH domain-only protein PHLDA3 is a novel p53-regulated repressor of Akt and a novel tumor suppressor of neuroendocrine tumors2014

    • Author(s)
      大木理恵子
    • Organizer
      16th International p53 workshop
    • Place of Presentation
      ストックホルム
    • Year and Date
      2014-06-15
    • Related Report
      2014 Research-status Report
  • [Patent(Industrial Property Rights)] 移植材料及びその調製方法2015

    • Inventor(s)
      大木理恵子、角昭一郎、坂田直昭
    • Industrial Property Rights Holder
      大木理恵子、角昭一郎、坂田直昭
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-05-22
    • Related Report
      2015 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] 移植材料及びその調製方法2014

    • Inventor(s)
      大木理恵子、角昭一郎、坂田直昭
    • Industrial Property Rights Holder
      大木理恵子、角昭一郎、坂田直昭
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2014-107529
    • Filing Date
      2014-05-23
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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