AhR plays a role in suppression of intestinal carcinogenesis

2011 Fiscal Year Final Research Report

• 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(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
• Keywords: 遺伝子 / 環境 / 癌 / シグナル伝達 / 炎症

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] 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
  • 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
  • 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
• [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
  • Year and Date: 20100100
• [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
  • Year and Date: 20091000
• [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
  • Year and Date: 20091000
• [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
  • Year and Date: 20091000
• [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
  • Year and Date: 20081200
• [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
  • Year and Date: 20080600
• [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.
  • Total Pages: 101-108
• [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)]。
• [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: 特願2010-027578号
  • Filing Date: 2010-02-10