• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Elucidation of Field Effect in Colorectal Cancer with Mutant KRAS

Research Project

Project/Area Number 24501322
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor biology
Research InstitutionFukuoka University

Principal Investigator

TSUNODA Toshiyuki  福岡大学, 医学部, 准教授 (70444817)

Co-Investigator(Renkei-kenkyūsha) NABESHIMA Kazuki  福岡大学医学部, 病理学, 教授 (40189189)
KAWADA Kenji  京都大学医学部, 消化管外科, 講師 (90322651)
SHIRASAWA Senji  福岡大学医学部, 細胞生物学, 教授 (10253535)
Research Collaborator OTA Yasuharu  
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsKRAS / 3次元培養 / 大腸癌 / 3次元培養 / 微小環境 / 薬剤スクリーニング / フィールドエフェクト / 大腸がん
Outline of Final Research Achievements

We have previously compared HKe3 cells, derived from colorectal cancer HCT116 cells and disrupted at mutated (mt) KRAS gene, with HCT116 cells in the 3D matrigel culture and found mtKRAS involvement in the inhibition of gene expressions associated with normal morphology. In this study, we found that mtKRAS specifically induced the dysregulated expressions of phosphodiesterase 4B (PDE4B), Alpha Kinase 2, miR-181, miR-210 and genes associated with the stroma ingredient etc. in 3D culture but not in 2D culture. Furthermore, we found that PDE4 inhibitors, including rolipram and resveratrol, induced luminal apoptosis in HCT116 spheroids. These results suggest that mtKRAS-mediated signaling in 3D environment is a target for cancer therapy and is also associated with cancer-stroma interaction (field effect).

Report

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

    (22 results)

All 2015 2014 2013 2012 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (9 results) Remarks (5 results)

  • [Journal Article] Zfat-deficient CD4⁺ CD8⁺ double-positive thymocytes are susceptible to apoptosis with deregulated activation of p38 and JNK.2015

    • Author(s)
      Ishikura S, Ogawa M, Doi K, Matsuzaki H, Iwaihara Y, Tanaka Y, Tsunoda T, Hideshima H, Okamura T, Shirasawa S.
    • Journal Title

      J Cell Biochem.

      Volume: 16(1) Issue: 1 Pages: 149-57

    • DOI

      10.1002/jcb.24954

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oncogenic Ras influences the expression of multiple lncRNAs.2014

    • Author(s)
      Kotake Y, Naemura M, Kitagawa K, Niida H, Tsunoda T, Shirasawa S, Kitagawa M.
    • Journal Title

      Cytotechnology.

      Volume: Dec.14

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Resveratrol induces luminal apoptosis of human colorectal cancer HCT116 cells in three-dimensional culture.2014

    • Author(s)
      Tsunoda T, Ishikura S, Doi K, Matsuzaki H, Iwaihara Y, Shirasawa S.
    • Journal Title

      Anticancer Res.

      Volume: 34(8) Pages: 4551-5

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Zfat-deficiency results in a loss of CD3zeta phosphorylation with dysregulation of ERK and Egr activities leading to impaired positive selection.2013

    • Author(s)
      Ogawa M, Okamura T, Ishikura S, Doi K, Matsuzaki H, Tanaka Y, Ota T, Hayakawa K, Suzuki H, Tsunoda T, Sasazuki T and Shirasawa S
    • Journal Title

      PLoS One

      Volume: 8

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Roles of ZFAT in haematopoiesis, angiogenesis and cancer development.2013

    • Author(s)
      Tsunoda T, Shirasawa S.
    • Journal Title

      Anticancer Res

      Volume: 33 Pages: 2833-2837

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] KRAS up-regulates the expression of miR-181a, miR-200c and miR-210 in a three-dimensional-specific manner in DLD-1 colorectal cancer cells.2012

    • Author(s)
      Ota T, Doi K, Fujimoto T, Tanaka Y, Ogawa M, Matsuzaki H, Kuroki M, Miyamoto S, Shirasawa S, Tsunoda T.
    • Journal Title

      Anticancer Res.

      Volume: 32 Pages: 2271-5

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] ALPK2 is crucial for luminal apoptosis and DNA repair-related gene expression in a three-dimensional colonic-crypt model.2012

    • Author(s)
      Yoshida Y, Tsunoda T, Doi K, Fujimoto T, Tanaka Y, Ota T, Ogawa M, Matsuzaki H, Kuroki M, Iwasaki A, Shirasawa S.
    • Journal Title

      Anticancer Res.

      Volume: 32 Pages: 2301-8

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibition of Phosphodiesterase-4 (PDE4) activity triggers luminal apoptosis and AKT dephosphorylation in a 3-D colonic-crypt model.2012

    • Author(s)
      Tsunoda T.
    • Journal Title

      Mol Cancer

      Volume: 11(1) Issue: 1 Pages: 46-46

    • DOI

      10.1186/1476-4598-11-46

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 膵臓癌のジェムシタビン耐性化には3次元特異的変異KRAS制御分子群が関与する2014

    • Author(s)
      角田俊之, 佐々木隆光, 土井佳子, 石倉周平, 白澤専二
    • Organizer
      第18回バイオ治療法研究会学術集会
    • Place of Presentation
      高松
    • Year and Date
      2014-12-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] 大腸癌スフェロイドにおける変異KRASカスケードの解明とその応用2014

    • Author(s)
      角田俊之, 白澤専二.
    • Organizer
      第2回細胞凝集研究会
    • Place of Presentation
      福岡
    • Year and Date
      2014-12-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] KRAS制御分子ALPK2の造腫瘍メカニズムの解析2014

    • Author(s)
      角田俊之, 土井佳子, 石倉周平, 白澤専二
    • Organizer
      日本人類遺伝学会第59回大会
    • Place of Presentation
      船堀
    • Year and Date
      2014-11-19 – 2014-11-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] 変異KRAS陽性癌を標的とする薬剤開発のためのスクリーニングシステム2014

    • Author(s)
      角田俊之, 白澤専二.
    • 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] 変異KRASが制御する3次元特異的癌増殖経路阻害のためのドラッグスクリーニング法の開発2014

    • Author(s)
      角田俊之, 土井佳子, 石倉周平, 白澤専二.
    • Organizer
      化学療法基盤支援活動第3回シンポジウム
    • Place of Presentation
      名護
    • Year and Date
      2014-05-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] PDE4の抑制は3次元大腸クリプトモデルにおいてアポトーシスとAKTの脱リン酸化を誘導する.2013

    • Author(s)
      角田俊之, 白澤専二
    • 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] 大腸癌における3次元特異的変異KRAS制御microRNAの解析2013

    • Author(s)
      角田俊之, 土井佳子, 石倉周平, 白澤専二
    • Organizer
      日本人類遺伝学会第58回大会
    • Place of Presentation
      仙台
    • Related Report
      2013 Research-status Report
  • [Presentation] 変異KRAS制御ALPK2は3次元大腸クリプトモデルにおいてアポトーシスとDNA修復関連遺伝子の発現を誘導する2012

    • Author(s)
      角田俊之
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌・ホテルロイトン札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] 大腸癌spheroidに対するPDE4阻害剤の効果検討

    • Author(s)
      角田俊之, 太田岳晴, 土井佳子, 石倉周平, 白澤専二
    • Organizer
      第17回バイオ治療法研究会学術集会
    • Place of Presentation
      福岡
    • Related Report
      2013 Research-status Report
  • [Remarks] 福岡大学医学部 細胞生物学教室

    • URL

      http://www.med.fukuoka-u.ac.jp/cellbio/top.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 先端分子医学研究所 (FCAM)

    • URL

      http://www.med.fukuoka-u.ac.jp/fcam-med/index.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 福岡大学基盤研究機関先端分子医学研究所ホームページ

    • URL

      http://www.med.fukuoka-u.ac.jp/fcam-med/index2.html

    • Related Report
      2013 Research-status Report
  • [Remarks] 福岡大学細胞生物学ホームページ

    • URL

      http://www.med.fukuoka-u.ac.jp/cellbio/top.html

    • Related Report
      2013 Research-status Report
  • [Remarks] 福岡大学医学部細胞生物学教室

    • URL

      http://cellbio-fukuoka-u.com/

    • Related Report
      2012 Research-status Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi