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

2008 Fiscal Year Final Research Report

• Project/Area Number: 19592162
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Kanagawa 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)
• Project Period (FY): 2007 – 2008
• 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

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。

Research Products

• [Journal Article] Roles of Collagen Molecules in Growth and Differentiation of Human Osteoblasts (2009)
  • Author(s): Maehata Y, Lee MC, Hata I
  • Journal Title: J Oral Bioscience 51(2) Pages: 72-80
  • Peer Reviewed
• [Journal Article] Heparin promotes the growth of human embryonic stem cells in a defined serum-free medium (2008)
  • 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
  • Peer Reviewed
• [Journal Article] p63(TP63)elicits strong trans-activation of the MFG-E8/lactadherin/BA46 gene through interactions between the TA and DeltaN isoforms (2008)
  • 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
  • Peer Reviewed
• [Journal Article] Integrins regulate mouse embryonic stem cell self-renewal (2007)
  • 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
  • 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, Ozawa S, Tsukuda M, Kubota E, Miyazaki K, St-Pierre Y, Hata
  • Journal Title: FEBS J 274(12) Pages: 3171-83
  • Peer Reviewed
• [Journal Article] Type III collagen is essential for growth acceleration of human osteoblastic cells by ascorbic acid 2-phosphate (2007)
  • 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
  • Peer Reviewed
• [Presentation] The BRAK box is opening (2009)
  • Author(s): Hata. R
  • Organizer: Yokosuka Science Festa 2009
  • Place of Presentation: Shonan Village Center
  • Year and Date: 20090604-07
• [Presentation] Production of BRAK knockout mice (2009)
  • Author(s): Nobuyuki Yajima, Ryu-Ichiro Hata
  • Organizer: Yokosuka Science Festa 2009
  • Place of Presentation: Shonan Village Center
  • Year and Date: 20090604-07
• [Presentation] Suppression of growth of Lewis lung carcinoma cell xenografts in BRAK transgenic mouse : Production of cancer resistant mouse (2009)
  • Author(s): Kazuhito Izukuri, Kenji Suzuki, Shigeyuki Ozawa, Eiro Kubota, Ryu-Ichiro Hata
  • Organizer: Yokosuka Science Festa 2009
  • Place of Presentation: Shonan Village Center
  • Year and Date: 20090604-07
• [Presentation] Chemokine BRAK stimulates apoptosis elicited by gefitinib in oral squamous cell carcinoma (2009)
  • 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
  • Year and Date: 20090604-07
• [Presentation] Expression of BRAK/CXCL14 is associated with antitumor efficacy of gefitinib in head and neck squamous cell carcinoma (2009)
  • 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
  • Year and Date: 20090604-07
• [Presentation] Functional analysis of promoter region of human BRAK/CXCL14, a tumor progression suppressor (2009)
  • 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
  • Year and Date: 20090604-07
• [Presentation] Functional Analysis of Promoter of Human BRAK/CXCL14, A Tumor Suppressor (2009)
  • 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
  • Year and Date: 20090401-04
• [Presentation] A new mechanism of tumor suppression by gefitinib in HNSCC (2009)
  • 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
  • Year and Date: 20090401-04
• [Presentation] Regulation of BRAK/CXCL14 gene expression by MAP kinase signaling (2008)
  • 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
  • Year and Date: 20081014-18
• [Presentation] Determination of transcription start-site of CXCL14/BRAK in squamous cell carcinoma (2008)
  • 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
  • Year and Date: 20080702-05
• [Presentation] p38 signaling up-regulates BRAK expression in squamous cell carcinoma (2008)
  • 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
  • Year and Date: 20080702-05
• [Presentation] Expression of BRAK/CXCL14 is a marker for gefitinib responsiveness of human head and neck squamous cell carcinoma (2008)
  • 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
  • Year and Date: 20080412-16
• [Presentation] Gefitinib (ZD1839, Iressa) reduced tumor volume through BRAK/CXCL14 expression in head and neck squamous cell carcinoma (2008)
  • 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
  • Year and Date: 20080113-18
• [Presentation] Reciprocal Effects of Oxidative Stress on the Gene Expression of Il-8/CXCL8 and BRAK/CXCL14 in Human Head and Neck Squamous Cell Carcinoma (2007)
  • 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
  • Year and Date: 20071201-05
• [Presentation] Gefitinib (ZD1839, Iressa) Reduces Tumor Volume Through BRAK/CXCL14 Expression (2007)
  • 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
  • Year and Date: 20071201-05
• [Presentation] Gefitinib stimulates expression of BRAK, a tumor suppressing chemokine and suppresses growth of tumor xenograft (2007)
  • 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
  • Year and Date: 20070520-25
• [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
• [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。