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Oral cancer model of functional mutations in NOTCH1 and HRAS

Research Project

Project/Area Number 15K11302
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Surgical dentistry
Research InstitutionTokai University

Principal Investigator

OTA Yoshihide  東海大学, 医学部, 教授 (60233152)

Co-Investigator(Kenkyū-buntansha) 木村 穣  東海大学, 医学部, 教授 (10146706)
青山 謙一  東海大学, 医学部, 助教 (10647530)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsNOTCH1 / Oral cancer / Mutation analysis / 口腔扁平上皮癌 / 大規模遺伝子解析 / NOTCH1変異 / HRAS変異 / 変異解析 / HRAS
Outline of Final Research Achievements

HEK293 cell lines expressing NOTCH1 wild type (WT cells) or p.A465T (A465T cells) were established. Flow cytometry indicated that NOTCH1 expression on the cell membrane was lower in A465T cells than that in WT cells. NOTCH1 and NICD were both detected by western blot in WT and A465T cells. The immunofluorescence signal for NICD was detected in the nucleus of WT cells, while it was localized mainly in the cytoplasm of A465T cells. HES1 and HEY1 mRNA expression levels were lower in A465T than in WT cells. The cell growth of WT cells was significantly higher than that of HEK293 cells (P < 0.01), while that of A465T cells was significantly lower than that of HEK293 cells (37%, P < 0.01). In a xenograft model, the tumor cell implantation rate of WT cells was 80%, while that of A465T cells was 0%.
This study indicates that NOTCH1 acts as an oncogene and that the NOTCH1 mutation (p.A465T) in the ligand-binding region causes the loss of tumorigenicity by downregulating the NOTCH1 pathway.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (11 results)

All 2018 2017 2016 2015

All Journal Article (6 results) (of which Peer Reviewed: 5 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Lateral retropharyngeal lymph node metastasis from squamous cell carcinoma of the upper gingiva: a case report2018

    • Author(s)
      Yamazaki H, Sasaki M, Aoyama K, Suzuki T, Denda Y, Uchibori M, Nakanishi Y, Kojima R, Ota Y
    • Journal Title

      MOLECULAR AND CLINICAL ONCOLOGY

      Volume: 8 Pages: 68-72

    • DOI

      10.3892/mco.2017.1496

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multicenter retrospective study of cetuximab plus platinum-based chemotherapy for recurrent or metastatic oral squamous cell carcinoma2018

    • Author(s)
      Yanamoto Souichi、Umeda Masahiro、Kioi Mitomu、Kirita Tadaaki、Yamashita Tetsuro、Hiratsuka Hiroyoshi、Yokoo Satoshi、Tanzawa Hideki、Uzawa Narikazu、Shibahara Takahiko、Ota Yoshihide、Kurita Hiroshi、Okura Masaya、Hamakawa Hiroyuki、Kusukawa Jingo、Tohnai Iwai
    • Journal Title

      Cancer Chemotherapy and Pharmacology

      Volume: 81 Issue: 3 Pages: 549-554

    • DOI

      10.1007/s00280-018-3531-x

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A mutation in NOTCH1 ligand binding region detected in patients with oral squamous cell carcinoma reduces NOTCH1 oncogenic effect2017

    • Author(s)
      M. Uchibori, Ken-ichi Aoyama, Y. Ota, K. Kajiwara, M. Tanaka, M. Kimura
    • Journal Title

      Oncology Reports

      Volume: 38 Issue: 4 Pages: 2237-2242

    • DOI

      10.3892/or.2017.5870

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Progression level of extracapsular spread and tumor budding for cervical lymph node metastasis of OSCC2017

    • Author(s)
      Yamada Shin-ichi、Otsuru Mitsunobu、Yanamoto Souichi、Hasegawa Takumi、Aizawa Hitoshi、Kamata Takahiro、Yamakawa Nobuhiro、Kohgo Tomoyuki、Ito Akira、Noda Yuri、Hirai Chihoko、Kitamura Tetsuya、Okura Masaya、
    • Journal Title

      Clinical Oral Investigations

      Volume: 22 Issue: 3 Pages: 1311-1318

    • DOI

      10.1007/s00784-017-2231-y

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Saliva pH affects the sweetness sense2017

    • Author(s)
      Ken-ichi Aoyama, Yuichiro Okino, Hiroshi Yamazaki, Rena Kojima, Masahiro Uchibori, Yasuhiro Nakanishi, Yoshihide Ota
    • Journal Title

      Nutrition

      Volume: 35 Pages: 51-55

    • DOI

      10.1016/j.nut.2016.10.018

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Kikuchi-Fujimoto Disease with 18F-Fludeoxyglucose Uptake in Cervical Lymph Nodes on Dual Time-point Imaging Positron Emission Tomography/Computed Tomography Mimicking Malignant Disease2017

    • Author(s)
      Ken-ichi Aoyama, Mitsunobu Otsuru, Masahiro Uchibori, Yoshihide Ota
    • Journal Title

      World J Nucl Med

      Volume: 16 Pages: 68-70

    • Related Report
      2016 Research-status Report
    • Open Access
  • [Presentation] Mutational landscape of Japanese oral squamous cell carcinoma2017

    • Author(s)
      青山謙一、太田嘉英、内堀雅博、梶原景正、木村穣
    • Organizer
      日本口腔外科学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 日本人口腔扁平上皮癌に見いだされた変異型NOTCH1分子の発現解析2016

    • Author(s)
      内堀 雅博, 太田 嘉英, 青山 謙一, 梶原 景正, 木村 穣
    • Organizer
      日本生化学会大会・日本分子生物学会年会合同大会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] 口腔扁平上皮癌由来の変異NOTCH1を導入したHEK293はNICDの発現と細胞増殖が低下する2016

    • Author(s)
      内堀 雅博, 青山 謙一, 太田 嘉英, 梶原 景正, 田中 正史, 木村 穣
    • Organizer
      日本癌学会総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] NOTCH1 mutation found in Japanese oral carcinoma2015

    • Author(s)
      KI Aoyama, Y Ota, M Uchibori, K Kajiwara, M kimura
    • Organizer
      European Cancer Congress 2015
    • Place of Presentation
      Wien Exhibition and Congress Center (オーストリア・ウィーン)
    • Year and Date
      2015-10-25
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] The functional analysis of NOTCH1 mutations found in Japanese oral carcinom2015

    • Author(s)
      KI Aoyama, Y Ota, M Uchibori, K Kajiwara, M kimura
    • Organizer
      日本癌学会学術大会
    • Place of Presentation
      名古屋国際会議場(愛知県、名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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