Tissue distribution of aryl hydrocarbon receptor in the intestine: Implication of putative roles in tumor suppression

Journal Article · Sun May 01 04:00:00 EDT 2016 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2016.03.012· OSTI ID:22648565

Ikuta, Togo ^[1]; Kurosumi, Masafumi ^[2]; Yatsuoka, Toshimasa ^[3]; Nishimura, Yoji ^[3]

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1. Department of Cancer Prevention, Research Institute for Clinical Oncology, Saitama Cancer Center, 818 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806 (Japan)
2. Division of Pathology, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806 (Japan)
3. Division of Gastroenterological Surgery, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806 (Japan)

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{sup 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. - Highlights: • In the normal intestine, AhR was mainly localized in stroma containing immune cells. • In the tumor tissue, AhR expression was found in both stromal and tumor cells. • AhR knockdown promoted cell growth in colon cancer cell lines.

• OSTI ID: 22648565
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 343; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

3-METHYLCHOLANTHRENE
60 APPLIED LIFE SCIENCES
ANIMAL TISSUES
CARCINOGENESIS
COMPLEXES
CULTURE MEDIA
CYTOPLASM
HOMEOSTASIS
IMMUNITY
INFLAMMATION
INHIBITION
INTERACTIONS
KYNURENINE
LARGE INTESTINE
LEAD
LIGANDS
METHANOL
MICE
MICROORGANISMS
NEOPLASMS
PLANT GROWTH
RECEPTORS
TISSUE DISTRIBUTION
TUMOR CELLS