A Protective Role of Aryl Hydrocarbon Receptor Repressor in Inflammation and Tumor Growth
Cancers 11 巻 5 号
589- 頁
2019-04-27 発行
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| ファイル情報(添付) | |
| タイトル ( eng ) |
A Protective Role of Aryl Hydrocarbon Receptor Repressor in Inflammation and Tumor Growth
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| 作成者 |
Vogel Christoph F. A.
Campbell Claire E.
Kado Sarah Y.
Nguyen-Chi Aimy
Sweeney Colleen
Pollet Marius
Haarmann-Stemmann Thomas
Tuscano Joseph M.
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| 収録物名 |
Cancers
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| 巻 | 11 |
| 号 | 5 |
| 開始ページ | 589 |
| 抄録 |
The aryl hydrocarbon receptor (AhR) is known for mediating the toxicity of environmental pollutants such as dioxins and numerous dioxin-like compounds, and is associated with the promotion of various malignancies, including lymphoma. The aryl hydrocarbon receptor repressor (AhRR), a ligand-independent, transcriptionally inactive AhR-like protein is known to repress AhR signaling through its ability to compete with the AhR for dimerization with the AhR nuclear translocator (ARNT). While AhRR effectively blocks AhR signaling, several aspects of the mechanism of AhRR’s functions are poorly understood, including suppression of inflammatory responses and its putative role as a tumor suppressor. In a transgenic mouse that overexpresses AhRR (AhRR Tg) we discovered that these mice suppress 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)- and inflammation-induced tumor growth after subcutaneous challenge of EL4 lymphoma cells. Using mouse embryonic fibroblasts (MEF) we found that AhRR overexpression suppresses the AhR-mediated anti-apoptotic response. The AhRR-mediated inhibition of apoptotic resistance was associated with a suppressed expression of interleukin (IL)-1β and cyclooxygenase (COX)-2, which was dependent on activation of protein kinase A (PKA) and the CAAT-enhancer-binding protein beta (C/EBPβ). These results provide mechanistic insights into the role of the AhRR to suppress inflammation and highlight the AhRR as a potential therapeutic target to suppress tumor growth.
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| 著者キーワード |
AhR
AhRR
carcinogenicity
C/EBPβ
cyclooxygenase 2
inflammation
interleukin 1
lymphoma
TCDD
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| 内容記述 |
Research reported in this publication is supported in part by the National Institute of Environmental Health Sciences of the National Institutes of Health under Award Number R01 ES029126 and R21 ES030419, the core center grant, P30-ES023513 from the National Institute of Environmental Health Sciences, and by the University of California Davis Cancer Center support grant P30 CA093373 and the Cancer Immunology Grant fund 48649. Its contents are solely the responsibility of the authors and do not necessarily represent the offcial views of the National Institutes of Health.
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| 言語 |
英語
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| 資源タイプ | 学術雑誌論文 |
| 出版者 |
MDPI
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| 発行日 | 2019-04-27 |
| 権利情報 |
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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| 出版タイプ | Version of Record（出版社版。早期公開を含む） |
| アクセス権 | オープンアクセス |
| 収録物識別子 |
[ISSN] 2072-6694
[DOI] 10.3390/cancers11050589
[PMID] 31035533
[DOI] https://doi.org/10.3390/cancers11050589
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