AhR plays a role in suppression of intestinal carcinogenesis

• Project/Area Number: 20390042
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Environmental pharmacy
• Research Institution: Research Institute for Clinical Oncology, Saitama Cancer Center
• Principal Investigator: KAWAJIRI Kaname 埼玉県立がんセンター, 臨床腫瘍研究所, 専門員 (50142112)
• Co-Investigator(Kenkyū-buntansha): 生田 統悟 埼玉県立がんセンター, 臨床腫瘍研究所, 主任研究員 (00262072) ; 小林 康人 埼玉県立がんセンター, 臨床腫瘍研究所, 研究員 (80425652)
• Co-Investigator(Renkei-kenkyūsha): IKUTA Togo 埼玉県立がんセンター, 臨床腫瘍研究所, 主任研究員 (00262072) ; KOBAYASHI Yasuhito 埼玉県立循環器・呼吸器病センター(現在) (80425652)
• Project Period (FY): 2008 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000); Fiscal Year 2011: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2009: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2008: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
• Keywords: 遺伝子 / 環境 / 癌 / シグナル伝達 / 炎症 / 発現制御

Research Abstract

The aryl hydrocarbon receptor(AhR) is a ligand-dependent transcription factor known to be involved in the promotion of chemical carcinogenesis. We demonstrated that AhR plays a tumor suppressor role in the intestine as an E3 ubiquitin ligase ofβ-catenin. Our findings suggest that chemoprevention with naturally-occurring and chemically-designed AhR ligands can be used to successfully prevent intestinal cancers.

Research Products

• [Journal Article] Cross-talk of dioxin and estrogen receptor signals through the ubiquitin system (2011)
  • Author(s): Ohtake, F., Fujii-Kuriyama, Y., Kawajiri, K., Kato, S.
  • Journal Title: J. Steroid Biochem. Mol. Biol Volume: 127 Pages: 102-107
  • Peer Reviewed
• [Journal Article] Cross-talk of dioxin and estrogen receptor signals through the ubiquitin system (2011)
  • Author(s): Ohtake, F., Fujii-Kuriyama, Y., Kawajiri, K., Kato, S.
  • Journal Title: J.Steroid Biochem.Mol.Biol. Volume: 127 Issue: 1-2 Pages: 102-107
  • DOI: 10.1016/j.jsbmb.2011.03.007
  • Peer Reviewed
• [Journal Article] Cross-talk of dioxin and estrogen receptor signals through the ubiquitin system. (2011)
  • Author(s): Ohtake, F., Fujii-Kuriyama, Y., Kawajiri, K., Kato, S.
  • Journal Title: J.Steroid Biochem.Mol.Biol.(Review) in press
  • Peer Reviewed
• [Journal Article] Cross-talk of dioxin and estrogen receptor signals through the ubiquitin system. (2011)
  • Author(s): Ohtake, F., Fujii-Kuriyama, Y., Kawajiri, K., Kato, S.
  • Journal Title: J.Steroid Biochem.Mol.Biol. Volume: (Review in press)
  • Peer Reviewed
• [Journal Article] Blymphocyte-induced maturation protein 1 is a novel target gene of aryl hydrocarbon receptor (2010)
  • Author(s): Ikuta, T., Ohba, M., Zouboulis, CC., Fujii-Kuriyama, Y., Kawajiri, K.
  • Journal Title: J. Dermatol. Sci Volume: 58 Pages: 211-216
  • NAID: 10027401221
  • Peer Reviewed
• [Journal Article] Molecular mechanisms of the physiological functions of the aryl hydrocarbon(dioxin) receptor, a multifunctional regulator that senses and responds to environmental stimuli (2010)
  • Author(s): Fujii-Kuriyama, Y., Kawajiri, K.
  • Journal Title: Proc Jpn. Acad. Ser Volume: B86 Pages: 40-53
  • NAID: 130000149632
  • Peer Reviewed
• [Journal Article] Blymphocyte-induced maturation protein 1 is a novel target gene of aryl hydrocarbon receptor. (2010)
  • Author(s): Ikuta, T., Ohba, M., Zouboulis, CC., Fujii-Kuriyama, Y., Kawajiri, K.
  • Journal Title: J.Dermatol.Sci. 58 Pages: 211-216
  • NAID: 10027401221
  • Peer Reviewed
• [Journal Article] Molecular mechanisms of the physiological functions of the aryl hydrocarbon (dioxin) receptor, a multifunctional regulator that senses and responds to environmental stimuli. (2010)
  • Author(s): Fujii-Kuriyama, Y., Kawajiri, K.
  • Journal Title: Proc.Jpn.Acad.Ser.B 86 Pages: 40-53
  • NAID: 130000149632
  • Peer Reviewed
• [Journal Article] B lymphocyte-induced maturation protein 1 is a novel target gene of aryl hydrocarbon receptor. (2010)
  • Author(s): Ikuta, T., Kawajiri, K., et.al.
  • Journal Title: J.Dermatol.Sci. Volume: 58 Pages: 211-216
  • NAID: 10027401221
  • Peer Reviewed
• [Journal Article] Molecular mechanisms of the physiological functions of the aryl hydrocarbon(dioxin)receptor, a multifunctional regulator that senses and responds to environmental stimuli (2010)
  • Author(s): Fujii-Kuriyama, Y., Kawajiri, K.
  • Journal Title: Proc.Jpn.Acad. Ser.B 86 Pages: 40-53
  • NAID: 130000149632
  • Peer Reviewed
• [Journal Article] B lymphocyte-induced maturation protein 1 is a novel target gene of aryl hydrocarbon receptor (2010)
  • Author(s): Ikuta, T., Kawajiri, K., et.al.
  • Journal Title: J.Dermatol.Sci. (in press)
  • NAID: 10027401221
  • Peer Reviewed
• [Journal Article] Hyper-sensitivity of aryl hydrocarbon receptor-deficient mice to lipopoly-saccharide-induced septic shock (2009)
  • Author(s): Sekine, H., Mimura, I., Oshima, M., Okawa, H., Kanno, J., Igarashi, K., Gonzalez, F. J., Ikuta, T., Kawajiri, K., and Fujii-Kuriyama, Y.
  • Journal Title: Mol Cell. Biol Volume: 29 Pages: 6391-6400
  • Peer Reviewed
• [Journal Article] Aryl hydrocarbon receptor suppresses intestinal carcinogenesis in ApcMin/+mice with natural ligands (2009)
  • Author(s): Kawajiri, K., Kobayashi, Y., Ohtake, F., Ikuta, T., Matsusihima, Y., Mumura, J., Petterson, S., Pollenz, R. S., Sakaki, T., Hirokawa, T., Kurosumi, M., Poellinger, L., Kato, S., and Fujii-Kuriyama, Y.
  • Journal Title: Proc Natl. Acad, Sci. USA Volume: 106 Pages: 13481-13486
  • Peer Reviewed
• [Journal Article] AhR protein trafficking and function in the skin (2009)
  • Author(s): Ikuta, T., Namiki, T., Fujii-Kuriyama, Y., and Kawajiri, K.
  • Journal Title: Biochem. Pharmacol Volume: 77 Pages: 588-596
  • Peer Reviewed
• [Journal Article] Hypersensitivity of aryl hydrocarbon receptor-deficient mice to lipopolysaccharide-induced septic shock. (2009)
  • Author(s): Sekine, H., Mimura, I., Oshima, M., Okawa, H., Kanno, J., Igarashi, K., Gonzalez, F.J., Ikuta, T., Kawajiri, K., Fujii-Kuriyama, Y.
  • Journal Title: Mol Cell.Biol. 29 Pages: 6391-6400
  • Peer Reviewed
• [Journal Article] Aryl hydrocarbon receptor suppresses intestinal carcinogenesis in Apc^<Min/+> mice with natural ligands. (2009)
  • Author(s): Kawajiri, K., Kobayashi, Y., Ohtake, F., Ikuta, T., Matsusihima, Y., Mumura, J., Petterson, S., Pollenz, R.S., Sakaki, T., Hirokawa, T., Kurosumi, M., Poellinger, L., Kato, S., Fujii-Kuriyama, Y.
  • Journal Title: Proc.Natl.Acad, Sci.USA. 106 Pages: 13481-13486
  • Peer Reviewed
• [Journal Article] AhR protein trafficking and function in the skin. (2009)
  • Author(s): Ikuta, T., Namiki, T., Fujii-Kuriyama, Y., Kawajiri, K.
  • Journal Title: Biochem.Pharmacol. 77 Pages: 588-596
  • Peer Reviewed
• [Journal Article] Aryl hydrocarbon receptor suppresses intestinal carcinogenesis in Apc^<Min/+> mice with natural ligands (2009)
  • Author(s): Kawajiri, K., Kobayashi, Y., Ikuta, T., Fujii-Kuriyama, Y., et al.
  • Journal Title: Proc.Natl.Acad, Sci.USA 106 Pages: 13481-13486
  • Peer Reviewed
• [Journal Article] Hypersensitivity of aryl hydrocarbon receptor-deficient mice to lippolysaccharide-induced septic shock (2009)
  • Author(s): Sekine, H., Ikuta, T., Kawajiri, K., et al.
  • Journal Title: Mol.Cell.Biol. 29 Pages: 6391-6400
  • Peer Reviewed
• [Journal Article] AhR protein trafficking and function in the skin (2009)
  • Author(s): Ikuta, T. Kawajiri, K., et al
  • Journal Title: Biochem. Pharmacol. 77 Pages: 588-596
  • Peer Reviewed
• [Journal Article] Persistent Organic Pollutants (POPS) Research in Asia (Ed. M. Morita) (2008)
  • Author(s): Fujii-Kuriyama, Y. Kawajiri, K., et al.
  • Journal Title: Mechanisms of toxicological and physiological actions of aryl hydrocarbon receptor (AHR) in mice Pages: 322-325
• [Presentation] AhR plays a role in suppression of intestinal carcinogenesis (2010)
  • Author(s): Kawajiri, Kaname
  • Organizer: The 15^<th> Charles Heidelberger International Symposium in Cancer Research
  • Place of Presentation: Phitsanulok, Thailand
• [Presentation] AhR plays a role in suppression of intestinal carcinogenesis. (2010)
  • Author(s): Kawajiri, Kaname
  • Organizer: The 15^<th> Charles Heidelberger International Symposium in Cancer Research.
  • Place of Presentation: Phitsanulok, Thailand
• [Presentation] AhRによる大腸がん抑制機構 (2009)
  • Author(s): 川尻要
  • Organizer: 第2回博多シンポジウム「内・外環境と生物応答」
  • Place of Presentation: 福岡
• [Presentation] AhR plays a role in suppression of intestinal carcinogenesis (2009)
  • Author(s): Kawajiri, Kaname
  • Organizer: HORIBA International Conference/CDBIM Symposium
  • Place of Presentation: The University of Tokyo,東京
• [Presentation] β-catenin accumulation and ASC-mediated inflammation promote cooperatively intestinal carcinogenesis in AhR-deficient mice (2009)
  • Author(s): Ikuta, T., Kobayashi, Y., Kitazawa, M., Sekine, H., Itano, N., Kurosumi, M., Fujii-Kuriyama, Y., Taniguchi, S., Kawajiri, K
  • Organizer: 第68回日本癌学会
  • Place of Presentation: 横浜
• [Presentation] AhR plays a role in suppression of intestinal carcinogenesis. (2009)
  • Author(s): Kawajiri, Kaname
  • Organizer: HORIBA International Conference/CDBIM Symposium
  • Place of Presentation: The University of Tokyo.(東京)
• [Presentation] AhR plays a role in suppression of intestinal carcinogenesis (2009)
  • Author(s): 川尻要
  • Organizer: HORIBA International Conference/CDBIM Symposium, The University of Tokyo
  • Place of Presentation: 東京
• [Presentation] AhR plays a role in suppression of intestinal carcinogenesis (2009)
  • Author(s): 川尻要
  • Organizer: Seminar in Cancer Science Institute of Singapore, National University of Singapore
  • Place of Presentation: Singapore
• [Presentation] Ahレセプター(AhR)リガンドによるBlimpp1 mRNAの増加 (2008)
  • Author(s): 生田統悟,大場基,川尻要
  • Organizer: 第31回日本分子生物学会年会、第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] Aryl hydrocarbon Receptor(AhR)の大腸がん抑制機能について (2008)
  • Author(s): 川尻要
  • Organizer: 第14回日本家族性腫瘍学会学術集会・シンポジウム
  • Place of Presentation: 東京
• [Presentation] Ahレセプター(AhR)リガンドによるBlimpp1 mRNAの誘導 (2008)
  • Author(s): 生田統悟,大場基,川尻要
  • Organizer: 第31回日本分子生物学会年会、第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] Aryl hydrocarbon Receptor (AhR)の大腸がん抑制機能について (2008)
  • Author(s): 川尻要
  • Organizer: 第14回日本家族性腫瘍学会学術集会・シンポジウム
  • Place of Presentation: 東京
• [Presentation] Ahレセプター(AhR)リガンドによる Blimp1 mRNAの誘導 (2008)
  • Author(s): 生田統悟, 川尻要等
  • Organizer: 第31回日本分子生物学会年会、第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Book] Regulation of AhR activity by the AhR repressor(AhRR). in The AH Receptor in Biology and Toxicology (2011)
  • Author(s): Fujii-Kuriyama Y, Kawajiri K.
• [Book] Regulation of AhR activity by the AhR repressor (AhRR) (2011)
  • Author(s): Fujii-Kuriyama Y, Kawajiri K
  • Publisher: in The AH Receptor in Biology and Toxicology, John Wiley & Sons.Inc
• [Book] in The AH Receptor in Biology and Toxicology (Regulation of AhR activity by the AhR Repressor (AhRR).)((ed.)R.Pohjanvirta) (2011)
  • Author(s): Fujii-Kuriyama, Y., Kawajiri, K.
  • Publisher: John Wiley & Sons, Inc.
• [Book] Persistent Organic Pollutants (POPS) Research in Asia (Mechanisms of toxicological and physiological actions of aryl hydrocarbon receptor (AHR) in mice.)(Ed.M.Morita) (2008)
  • Author(s): Fujii-Kuriyama, Y.Kawajiri, K., et al.
• [Remarks] (1)[PNAS, 106, 13481-13486(2009)]への論文発表を受けて、「発がん予防につながる新たな大腸がん抑制機構を発見-緑黄色野菜は大腸がん予防効果があることの理由-」の報道発表を平成21年7月31日に埼玉県庁記者クラブで行った。その詳細は埼玉県政ニュース平成21年7月31日に掲載された。報道発表を受け、同日のNHKニュース、テレビ埼玉で報道される。8月1日、毎日、読売、産経、埼玉新聞などで報道される。
• [Remarks] (2) PNASに発表した論文がScience-Business eXchange(BioCentury & Nature)に取り上げられた[SciBX, 2(No.35), 11,(2009)]。
• [Remarks] [PNAS, 106, 13481-13486(2009)]への論文発表を受けて、「発がん予防につながる新たな大腸がん抑制機構を発見-緑黄色野菜は大腸がん予防効果があることの理由-」の報道発表を平成21年7月31日に埼玉県庁記者クラブで行った。その詳細は埼玉県政ニュース平成21年7月31日に掲載された。報道発表を受け、同日のNHKニュース、テレビ埼玉で報道される。8月1日、毎日、読売、産経、埼玉新聞などで報道される。
• [Remarks] PNASに発表した論文がScience-Business eXchange (BioCentury & Nature)に取り上げられた[SciBX, 2(No.35),11,(2009)]。
• [Patent(Industrial Property Rights)] 腸がん抑制剤及び腸がん抑制作用を有する物質のスクリーニング方法 (2010)
  • Inventor(s): 川尻要
  • Industrial Property Rights Holder: 埼玉県
  • Industrial Property Number: 2010-027578
  • Filing Date: 2010-02-10