Aryl Hydrocarbon Receptor Suppresses Intestinal Carcinogenesis in Apcmin/؉ Mice with Natural Ligands
Aryl hydrocarbon receptor suppresses intestinal carcinogenesis in ApcMin/؉ mice with natural ligands Kaname Kawajiria,1, Yasuhito Kobayashib, Fumiaki Ohtakec,d, Togo Ikutaa, Yoshibumi Matsushimaa, Junsei Mimurae, Sven Petterssonf, Richard S. Pollenzg, Toshiyuki Sakakih, Takatsugu Hirokawai, Tetsu Akiyamad, Masafumi Kurosumib, Lorenz Poellingerj, Shigeaki Katoc,d, and Yoshiaki Fujii-Kuriyamac,e aResearch Institute for Clinical Oncology and bHospital, Saitama Cancer Center, 818 Komuro, Ina, Saitama, 362-0806, Japan; cExploratory Research for Advanced Technology and Solution Oriented Research for Science and Technology, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan; dInstitute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan; eTsukuba Advanced Research Alliance Center, University of Tsukuba, Tennodai, Tsukuba, Ibaraki, 305-8577, Japan; fGerm-Free Facility and jDepartment of Cell and Molecular Biology, Karolinska Institute, S-171 77 Stockholm, Sweden; gDepartment of Biology, University of South Florida, Tampa, FL 33620; hDepartment of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama, 939-0398, Japan; and iComputational Biology Research Center, National Institute of Advanced Industrial Science and Technology, 2-42 Aomi, Koto-ku, Tokyo, 135-0064, Japan Edited by Tadatsugu Taniguchi, University of Tokyo, Tokyo, Japan, and approved June 23, 2009 (received for review February 26, 2009) Intestinal cancer is one of the most common human cancers. reported for some tumor suppressor gene products, such as VHL Aberrant activation of the canonical Wnt signaling cascade, for (11) and adenomatous polyposis coli (APC) (12). Also, the example, caused by adenomatous polyposis coli (APC) gene mu- natural AhR ligands of indole derivatives (13, 14), such as tations, leads to increased stabilization and accumulation of indole-3-acetic acid (IAA, so-called plant auxin), indole-3- -catenin, resulting in initiation of intestinal carcinogenesis.
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