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Regulation of gene expression of BRAK, a human tumor progression suppressing chemokine

Research Project

Project/Area Number 19592162
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionKanagawa Dental College

Principal Investigator

HATA Ryuuichirou  Kanagawa Dental College, 歯学部, 教授 (10014276)

Co-Investigator(Kenkyū-buntansha) OZAWA Shigeyuki  神奈川歯科大学, 歯学部, 特別研究員 (40434394)
MAEHATA Yojiro  神奈川歯科大学, 歯学部, 助教 (80410009)
TAKAGAKI Yuko  神奈川歯科大学, 歯学部, 准教授 (60050689)
バワール ウジャール  神奈川歯科大学, 歯学部, 特別研究員 (50433339)
加藤 靖正  神奈川歯科大学, 歯学部, 講師 (50214408)
倉田 俊一  神奈川歯科大学, 歯学部, 客員教授 (60140901)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords口腔癌 / 腫瘍抑制因子 / BRAK / CXCL14 / 転写制御 / ゲフィチニブ / 頭頚部癌 / 上皮増殖因子阻害剤 / 腫瘍抑制遺伝子 / CXCL14遺伝子 / AP-1結合配列 / 頭頸部癌 / ケモカイン / MAPキナーゼ / 上皮増殖因子
Research Abstract

口腔癌の進展を抑制する因子としてケモカインBRAK/CXCL14を見いだした。腫瘍組織ではBRAK/CXCL14の発現量が低下しているが、腫瘍細胞にBRAK/CXCL14を強制的に発現させると、腫瘍形成能が低下した。また、T細胞を欠損したヌードマウスに腫瘍を移植後、上皮増殖因子受容体の阻害剤であるゲフィチニブ(イレッサ)を飲ませると腫瘍内のBRAK/CXCL14の発現が上昇し、かつ腫瘍が小さくなった。BRAK/CXCL14の発現が腫瘍抑制に重要であると考えられるのでその遺伝子の発現制御機構を明らかにした。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (43 results)

All 2009 2008 2007 Other

All Journal Article (13 results) (of which Peer Reviewed: 13 results) Presentation (28 results) Remarks (2 results)

  • [Journal Article] Roles of Collagen Molecules in Growth and Differentiation of Human Osteoblasts2009

    • Author(s)
      Maehata Y, Lee MC, Hata I
    • Journal Title

      J Oral Bioscience 51(2)

      Pages: 72-80

    • NAID

      10027104531

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Heparin promotes the growth of human embryonic stem cells in a defined serum-free medium2008

    • Author(s)
      Furue MK, Na J, Jackson JP, Okamoto T, Jones M, Baker D, Hata. Moore HD, Sato JD, Andrews PW
    • Journal Title

      Proc Natl Acad Sci USA 105(36)

      Pages: 13409-14

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] p63(TP63)elicits strong trans-activation of the MFG-E8/lactadherin/BA46 gene through interactions between the TA and DeltaN isoforms2008

    • Author(s)
      Okuyama T, Kurata S, Tomimori Y, Fukunishi N, Sato S, Osada M, Tsukinoki K, Jin HF, Yamashita A, Ito M, Kobayashi S, Hata R.I, Ikawa Y, Katoh I.
    • Journal Title

      Oncogene 27

      Pages: 308-317

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Heparin promotes the growth of human embryonic stem cells in adefined serum-free medium.2008

    • Author(s)
      Furue MK., et al.
    • Journal Title

      Proc Natl Acad Sci USA. 105

      Pages: 13409-13414

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chemokine BRAK Stimulates Apoptosis of Oral Squamous Cell Carcinoma Caused by Gefitinib.2008

    • Author(s)
      Ito S., et al.
    • Journal Title

      Bull. Kanagawa Dent. Col. 36

      Pages: 87-89

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Determination of Transcriptional Start Site and Promoter Sequence of BRAK/CXCL14 Gene.2008

    • Author(s)
      Komori R., et al.
    • Journal Title

      Bull. Kanagawa Dent. Col. 36

      Pages: 90-92

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] p63(TP63)elicits strong trans-activation of the MFG-E8/lactadherin/BA46 genethrough interactions between the TA and DeltaN isoforms.2008

    • Author(s)
      Okuyama T., et. al.
    • Journal Title

      Oncogene 27(3)

      Pages: 308-317

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Integrins regulate mouse embryonic stem cell self-renewal2007

    • Author(s)
      Hayashi Y, Furue MK, Okamoto T, Ohnuma K, Myoishi Y, Fukuhara Y, Abe T, Sato JD, Hata, Asashima M
    • Journal Title

      Stem Cells 25(12)

      Pages: 3005-15

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Acidic extracellular pH increases calcium influx-triggered phospholipase D activity along with acidic sphingomyelinase activation to induce matrix metalloproteinase-9 expression in mouse metastatic melanoma2007

    • Author(s)
      Kato Y, Ozawa S, Tsukuda M, Kubota E, Miyazaki K, St-Pierre Y, Hata
    • Journal Title

      FEBS J 274(12)

      Pages: 3171-83

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Type III collagen is essential for growth acceleration of human osteoblastic cells by ascorbic acid 2-phosphate2007

    • Author(s)
      Maehata Y, Takamizawa S, Ozawa S, Izukuri K, Kato Y, Sato S, Lee MC, Kimura A, Hata
    • Journal Title

      long-acting vitamin C derivative. Matrix Biol 26(5)

      Pages: 371-81

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Integrins regulate mouse embryonic stem cell self-renewal.2007

    • Author(s)
      Hayashi Y., et. al.
    • Journal Title

      Stem Cells 12

      Pages: 3005-3015

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acidic extracellular pH increases calcium influx-triggered phospholipase D activity along with acidic sphingomyelinase activation to induce matrix metalloproteinase-9 expression in mouse metastatic melanoma.2007

    • Author(s)
      Kato Y., et. al.
    • Journal Title

      FEBS Journal 274(12)

      Pages: 3171-3183

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Type III collagen is essential for growth acceleration of human osteoblastic cells by ascorbic acid 2-phosphate, a long-acting vitamin C derivative.2007

    • Author(s)
      Maehata Y., et. al.
    • Journal Title

      Matrix Biology 26

      Pages: 371-378

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Functional Analysis of Promoter of Human BRAK/CXCL14, A Tumor Suppressor.2009

    • Author(s)
      Komori R., et al.
    • Organizer
      87^<th>IADR/Unilever Hatton Awards Competition Senior. (Basic. Science)
    • Place of Presentation
      Miami, Florida, USA.
    • Year and Date
      2009-03-31
    • Related Report
      2008 Annual Research Report
  • [Presentation] The BRAK box is opening2009

    • Author(s)
      Hata. R
    • Organizer
      Yokosuka Science Festa 2009
    • Place of Presentation
      Shonan Village Center
    • Related Report
      2008 Final Research Report
  • [Presentation] Production of BRAK knockout mice2009

    • Author(s)
      Nobuyuki Yajima, Ryu-Ichiro Hata
    • Organizer
      Yokosuka Science Festa 2009
    • Place of Presentation
      Shonan Village Center
    • Related Report
      2008 Final Research Report
  • [Presentation] Suppression of growth of Lewis lung carcinoma cell xenografts in BRAK transgenic mouse : Production of cancer resistant mouse2009

    • Author(s)
      Kazuhito Izukuri, Kenji Suzuki, Shigeyuki Ozawa, Eiro Kubota, Ryu-Ichiro Hata
    • Organizer
      Yokosuka Science Festa 2009
    • Place of Presentation
      Shonan Village Center
    • Related Report
      2008 Final Research Report
  • [Presentation] Chemokine BRAK stimulates apoptosis elicited by gefitinib in oral squamous cell carcinoma2009

    • Author(s)
      Shin Ito, Shigeyuki Ozawa, Naoto Shiiki, Keiichi Tsukinoki, Eiro Kubota, Yasumasa Kato, Takahide Taguchi, Yukari Imagawa-Ishiguro, Mamoru Tsukuda, and Ryu-Ichiro Hata
    • Organizer
      Yokosuka Science Festa 2009
    • Place of Presentation
      Shonan Village Center
    • Related Report
      2008 Final Research Report
  • [Presentation] Expression of BRAK/CXCL14 is associated with antitumor efficacy of gefitinib in head and neck squamous cell carcinoma2009

    • Author(s)
      Shigeyuki Ozawa, Yasumasa Kato, Shin Ito, Reika Komori, Kenji Suzuki, Keiichi Tsukinoki, Yojiro Maehata, Takahide Taguchi, Yukari Imagawa-Ishiguro, Mamoru Tsukuda, Eiro Kubota, and Ryu-Ichiro Hata
    • Organizer
      Yokosuka Science Festa 2009
    • Place of Presentation
      Shonan Village Center
    • Related Report
      2008 Final Research Report
  • [Presentation] Functional analysis of promoter region of human BRAK/CXCL14, a tumor progression suppressor2009

    • Author(s)
      Reika Komori, Shigeyuki Ozawa, Yasumasa Kato, Hisaaki Shinji, Shigenari Kimoto, and Ryu-Ichiro Hata
    • Organizer
      Yokosuka Science Festa 2009
    • Place of Presentation
      Shonan Village Center
    • Related Report
      2008 Final Research Report
  • [Presentation] Functional Analysis of Promoter of Human BRAK/CXCL14, A Tumor Suppressor2009

    • Author(s)
      Reika Komori Shigeyuki Ozawa, Yasumasa Kato, Hisaaki Shinji, Shigenari Kimoto, and Ryu-Ichiro Hata
    • Organizer
      87^<th> General Session & Exhibition of the IADR
    • Place of Presentation
      Miami, Florida
    • Related Report
      2008 Final Research Report
  • [Presentation] A new mechanism of tumor suppression by gefitinib in HNSCC2009

    • Author(s)
      Shigeyuki Ozawa, Yasumasa Kato, Shin Ito, Reika Komori, Naoto Shiiki, Keiichi Tukinoki, Satoru Ozono, Yojiro Maehata, Takahide Taguchi, Yukari Imagawa-Ishiguro, Mamoru Tsukuda, Eiro Kubota, and Ryu-Ichiro Hata
    • Organizer
      87^<th> General Session & Exhibition of the IADR
    • Place of Presentation
      Miami, Florida
    • Related Report
      2008 Final Research Report
  • [Presentation] Regulation of BRAK/CXCL14 gene expression by MAP kinase signaling2008

    • Author(s)
      Ryu-Ichiro Hata, Shigeyuki Ozawa, Yasumasa Kato, Shin Ito, Reika Komori, Yojiro Maehata, Eiro Kubota
    • Organizer
      AACR Special Conference : Chemical and Biological Aspects of Inflammation and Cancer
    • Place of Presentation
      Oahu, Hawaii
    • Related Report
      2008 Final Research Report
  • [Presentation] Expression of BRAK/CXCL14 is a marker for gefitinib responsiveness of human head and neck squamous cell carcinoma2008

    • Author(s)
      Ryu-Ichiro Hata, Shigeyuki Ozawa, Yasumasa Kato, Shin Ito, Reika Komori, Naoto Shiiki, Keiichi Tsukinoki, Satoru Ozono, Yojiro Maehata, Takahide Taguchi, Yukari Imagawa-Ishiguro, Mamoru Tsukuda, Eiro Kubota
    • Organizer
      American Association for Cancer Research Annual Meeting 2008
    • Place of Presentation
      San Diego, CA
    • Related Report
      2008 Final Research Report
  • [Presentation] Determination of transcription start-site of CXCL14/BRAK in squamous cell carcinoma2008

    • Author(s)
      Reika Komori Shigeyuki Ozawa, Yasumasa Kato, Hisaaki Shinji, Shigenari Kimoto, and Ryu-Ichiro Hata
    • Organizer
      86^<th> International Association of Dental Research
    • Place of Presentation
      Toronto, Canada
    • Related Report
      2008 Final Research Report
  • [Presentation] p38 signaling up-regulates BRAK expression in squamous cell carcinoma2008

    • Author(s)
      Shigeyuki Ozawa, Yasumasa Kato, Shin Ito, Reika Komori, Yojiro Maehata, Eiro Kubota, and Ryu-Ichiro Hata.
    • Organizer
      86^<th> International Association of Dental Research
    • Place of Presentation
      Toronto, Canada
    • Related Report
      2008 Final Research Report
  • [Presentation] Gefitinib (ZD1839, Iressa) reduced tumor volume through BRAK/CXCL14 expression in head and neck squamous cell carcinoma2008

    • Author(s)
      Shigeyuki Ozawa Yasumasa Kato, Shin Ito, Reika Komori, Naoto Shiiki, Keiichi Tukinoki, Satoru Ozono, Yojiro Maehata, Takahide Taguchi, Yukari Imagawa-Ishiguro, Mamoru Tsukuda, Eiro Kubota, and Ryu-Ichiro Hata
    • Organizer
      KEYSTONE SYMPOSIUM on chemokine and chemokine receptors
    • Place of Presentation
      Keystone, Colorado
    • Related Report
      2008 Final Research Report
  • [Presentation] Expression of BRAK/CXCL14 is a marker for gefitinib responsiveness ofhuman head and neck squamous cell carcinoma.2008

    • Author(s)
      Hata R., et al.
    • Organizer
      AACR Annual Meeting.
    • Place of Presentation
      San Diego, CA. USA.
    • Related Report
      2008 Annual Research Report
  • [Presentation] TypeIII collagen regulates growth of human osteoblastic cells.2008

    • Author(s)
      Maehata Y., et al.
    • Organizer
      86^<th> IADR.
    • Place of Presentation
      Toronto, Canada.
    • Related Report
      2008 Annual Research Report
  • [Presentation] p38 signaling up-regulates BRAK expression in squamous cell carcinoma.2008

    • Author(s)
      Ozawa S., et al.
    • Organizer
      86^<th> IADR.
    • Place of Presentation
      Toronto, Canada.
    • Related Report
      2008 Annual Research Report
  • [Presentation] Determination of transcription start-site of CXCL14/BRAK in squamouscell carcinoma.2008

    • Author(s)
      Komori R., et al.
    • Organizer
      86^<th> IADR.
    • Place of Presentation
      Toronto, Canada.
    • Related Report
      2008 Annual Research Report
  • [Presentation] Distinct roles of NF-κB Subunits in Matrix Metalloproteinase-9 Expression Induced by Acidic Extracellular pH.2008

    • Author(s)
      Kato Y., et al.
    • Organizer
      MRS AACR.
    • Place of Presentation
      Vancouver, Canada.
    • Related Report
      2008 Annual Research Report
  • [Presentation] Regulation of BRAK/CXCL14 gene expression by MAP kinase signaling.2008

    • Author(s)
      Hata R., et al.
    • Organizer
      AACR Special Conference : Chemical and Biological Aspects of Inflammation and Cancer.
    • Place of Presentation
      Ko Olina Oahu, Hawaii, USA.
    • Related Report
      2008 Annual Research Report
  • [Presentation] Reciprocal Effects of Oxidative Stress on the Gene Expression of Il-8/CXCL8 and BRAK/CXCL14 in Human Head and Neck Squamous Cell Carcinoma2007

    • Author(s)
      Maehata Y, Takamizawa S, Ozawa S, Kato Y, Yoshino F, Kobayashi K, Takahashi S, Todoki K, Hata, Lee M-C.
    • Organizer
      The 4th Joint Meeting of the Society For Free Radical Research Australia and Japan
    • Place of Presentation
      Kyoto, Japan
    • Related Report
      2008 Final Research Report
  • [Presentation] Gefitinib (ZD1839, Iressa) Reduces Tumor Volume Through BRAK/CXCL14 Expression2007

    • Author(s)
      Hata R, Ozawa S, Kato Y, Ito S, Komori R, Shiiki N, Tsukinoki K, Ozono S, Maehata Y, Taguchi T, Imagawa-Ishiguro Y, Tsukuda M, Kubota E
    • Organizer
      ASCB
    • Place of Presentation
      Washington DC, USA
    • Related Report
      2008 Final Research Report
  • [Presentation] Gefitinib stimulates expression of BRAK, a tumor suppressing chemokine and suppresses growth of tumor xenograft2007

    • Author(s)
      Hata R, Ozawa S, Kato Y, Komori R, Maehata Y, Kubota E, Tsukuda M
    • Organizer
      GRC on Cancer Genetics & Epigenetics IL CIOCCO
    • Place of Presentation
      Italy
    • Related Report
      2008 Final Research Report
  • [Presentation] Gefitinib stimulates expression of BRAK, a tumor suppressing chemokine and suppresses growth of tumor xenograft.2007

    • Author(s)
      Hata R., et. al.
    • Organizer
      GRC on Cancer Genetics & Epigenetics
    • Place of Presentation
      Italy
    • Related Report
      2007 Annual Research Report
  • [Presentation] Reconsideration of collagen function in human osteoblasts.2007

    • Author(s)
      Hata R., et. al.
    • Organizer
      Gordon Research Conference on Collagen
    • Place of Presentation
      USA
    • Related Report
      2007 Annual Research Report
  • [Presentation] Type III collagen is essential for growth acceleration of human osteoblastic cells.2007

    • Author(s)
      Maehata Y., et. al.
    • Organizer
      7th PPCTSS.
    • Place of Presentation
      Australia
    • Related Report
      2007 Annual Research Report
  • [Presentation] Gefitinib(ZD1839, Iressa)Reduces Tumor Volume Through BRAK/CXCL14E xpression.2007

    • Author(s)
      Hata R., et. al.
    • Organizer
      ASCB
    • Place of Presentation
      USA
    • Related Report
      2007 Annual Research Report
  • [Presentation] Development of Defined Medium for Human ES Cell Culture.2007

    • Author(s)
      Furue M K., et. al.
    • Organizer
      5th Annual Meeting of International Society for Stem Cell Research
    • Place of Presentation
      Australia
    • Related Report
      2007 Annual Research Report
  • [Remarks] 畑隆一郎、小澤重幸、加藤靖正、小森令賀、前畑洋次郎、久保田英朗 : 新しい発想による内在性癌進展抑制遺伝子の探索と発見~ケモカインBRAK/CXCL14はin vivoにおいて腫瘍抑制作用を示す~バイオアカデミックフォーラム、2007年6月20日~22日、東京ビッグサイト、東京テレビ

    • Related Report
      2008 Final Research Report
  • [Remarks] 小森令賀がIADR Hatton Awardで2008年度Travel Awardを受賞した。また、YokosukaScience Festa 2009でYoung Investigator Awardを受賞した、前畑洋次郎が2008年度歯科基礎医学会賞を受賞した。また、2009年度結合組織学会大高賞を受賞した。畑隆一郎が2009年度に本結合組織学会学術賞を受賞した。

    • Related Report
      2008 Final Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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