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イタノ ナオキ
ITANO NAOKI
板野 直樹 所属 京都産業大学 生命科学部 先端生命科学科 職種 教授 |
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| 言語種別 | 英語 |
| 発行・発表の年月 | 2013/07 |
| 形態種別 | 研究論文 |
| 査読 | 査読あり |
| 標題 | ASC-associated inflammation promotes cecal tumorigenesis in aryl hydrocarbon receptor-deficient mice |
| 執筆形態 | その他 |
| 掲載誌名 | CARCINOGENESIS |
| 出版社・発行元 | OXFORD UNIV PRESS |
| 巻・号・頁 | 34(7),pp.1620-1627 |
| 著者・共著者 | Togo Ikuta,Yasuhito Kobayashi,Masato Kitazawa,Kazuhiro Shiizaki,Naoki Itano,Tetsuo Noda,Sven Pettersson,Lorenz Poellinger,Yoshiaki Fujii-Kuriyama,Shun'ichiro Taniguchi,Kaname Kawajiri |
| 概要 | The aryl hydrocarbon receptor (AhR) plays a suppressive role in cecal carcinogenesis by CUL4B/AhR-mediated ubiquitylation and degradation of -catenin, which is activated by xenobiotics and natural ligands. AhR-deficient (AhR(/)) mice develop cecal tumors with severe inflammation. To elucidate whether the tumors develop autonomously in AhR(/) mice due to impaired -catenin degradation or in association with accelerated inflammation, we performed two kinds of experiments using germ-free (GF) AhR(/) mice and compound mutant mice lacking genes for AhR and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), which plays an essential role in caspase-1 activation in inflammasomes. Both GF AhR(/) and AhR(/)ASC(/) mice showed considerably reduced tumor development compared with that in AhR(/) mice albeit in a cancer-prone state with aberrant -catenin accumulation. Blocking of the interleukin (IL)-1 signaling pathway by treatment with a caspase-1 inhibitor, YVAD, reduced cecal tumorigenesis in AhR(/) mice. Signal transducers and activators of transcription 3 (STAT3) activation was detected in the cecal epithelium of the AhR(/) mice due to enhanced IL-6 production. An inhibitor of the STAT3 signaling pathway, AG490 suppressed the tumor formation. ASC-mediated inflammation was also found to play a critical role in tumor development in Apc(Min/) mice, a mouse model of familial adenomatous polyposis. Collectively, these results revealed an important role of the bacteria-triggered or ASC-mediated inflammation signaling pathway in the intestinal tumorigenesis of mice and suggest a possible chemical therapeutic intervention, including AhR ligands and inhibitors of the inflammation pathway. |
| DOI | 10.1093/carcin/bgt083 |
| ISSN | 0143-3334/1460-2180 |