title: Tissue distribution of aryl hydrocarbon receptor in the intestine: Implication of putative roles in tumor suppression.
abstract: Intestinal homeostasis is maintained by complex interactions between intestinal microorganisms and the gut immune system. Dysregulation of gut immunity may lead to inflammatory disorders and tumorigenesis. We previously have shown the tumor suppressive effects of aryl hydrocarbon receptor (AhR) in intestinal carcinogenesis. In the present study, we investigated AhR distribution in the mouse and human intestine by histochemical analysis. In the normal intestine, AhR was mainly localized in the stroma containing immune cells in the lamina propria and lymphoid follicles. On the other hand, in the tumor tissue from human colon cancer and that developed in Apc(Min/+)mice, AhR expression was elevated. AhR immunostaining was found in both stromal and tumor cells. Although AhR was localized in the cytoplasm of tumor cells in most cases, nuclear AhR was also observed in some. AhR knockdown using siRNA resulted in significant promotion of cell growth in colon cancer cell lines. Furthermore, AhR activation by AhR ligands supplemented in culture medium suppressed cell growth. Our study results suggest that tumor suppressive roles of AhR are estimated in two distinct ways: in normal tissue, AhR is associated with tumor prevention by regulating gut immunity, whereas in tumor cells, it is involved in growth suppression.
authors.affiliation: Department of Cancer Prevention, Research Institute for Clinical Oncology, Saitama Cancer Center, 818 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806, Japan. Electronic address: togo@cancer-c.pref.saitama.jp.
authors.forename: Togo
authors.initials: T
authors.lastname: Ikuta
authors.affiliation: Division of Pathology, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806, Japan. Electronic address: mkurosumi@cancer-c.pref.saitama.jp.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kurosumi
authors.affiliation: Division of Gastroenterological Surgery, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806, Japan. Electronic address: yatsuoka-gi@umin.ac.jp.
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Yatsuoka
authors.affiliation: Division of Gastroenterological Surgery, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806, Japan. Electronic address: yojinish@cancr-c.pref.saitama.jp.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Nishimura
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007414:Intestinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D007422:Intestines / Q000166:cytology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D012004:Rectal Neoplasms / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D014018:Tissue Distribution; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018336:Receptors, Aryl Hydrocarbon; D025521:Tumor Suppressor Proteins
keywords: Aryl Hydrocarbon receptor; Colon cancer; Gut immunity; Tumor suppression