Regulation of IDO2 by the Aryl Hydrocarbon Receptor (AhR) in Breast Cancer
Indoleamine 2,3-dioxygenase 2 (IDO2) is a tryptophan-catabolizing enzyme and a homolog of IDO1 with a distinct expression pattern compared with IDO1. In dendritic cells (DCs), IDO activity and the resulting changes in tryptophan level regulate T-cell differentiation and promote immune tolerance. Rec...
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MDPI AG
2023-05-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/10/1433 |
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| author | Sarah Y. Kado Keith Bein Alejandro R. Castaneda Arshia A. Pouraryan Nicole Garrity Yasuhiro Ishihara Andrea Rossi Thomas Haarmann-Stemmann Colleen A. Sweeney Christoph F. A. Vogel |
| author_facet | Sarah Y. Kado Keith Bein Alejandro R. Castaneda Arshia A. Pouraryan Nicole Garrity Yasuhiro Ishihara Andrea Rossi Thomas Haarmann-Stemmann Colleen A. Sweeney Christoph F. A. Vogel |
| author_sort | Sarah Y. Kado |
| collection | DOAJ |
| description | Indoleamine 2,3-dioxygenase 2 (IDO2) is a tryptophan-catabolizing enzyme and a homolog of IDO1 with a distinct expression pattern compared with IDO1. In dendritic cells (DCs), IDO activity and the resulting changes in tryptophan level regulate T-cell differentiation and promote immune tolerance. Recent studies indicate that IDO2 exerts an additional, non-enzymatic function and pro-inflammatory activity, which may play an important role in diseases such as autoimmunity and cancer. Here, we investigated the impact of aryl hydrocarbon receptor (AhR) activation by endogenous compounds and environmental pollutants on the expression of IDO2. Treatment with AhR ligands induced IDO2 in MCF-7 wildtype cells but not in CRISPR-cas9 AhR-knockout MCF-7 cells. Promoter analysis with IDO2 reporter constructs revealed that the AhR-dependent induction of IDO2 involves a short-tandem repeat containing four core sequences of a xenobiotic response element (XRE) upstream of the start site of the human <i>ido2</i> gene. The analysis of breast cancer datasets revealed that IDO2 expression increased in breast cancer compared with normal samples. Our findings suggest that the AhR-mediated expression of IDO2 in breast cancer could contribute to a pro-tumorigenic microenvironment in breast cancer. |
| first_indexed | 2024-03-11T03:51:09Z |
| format | Article |
| id | doaj.art-d29eb63d4d5e40e3a3c2b8a250f9ab18 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T03:51:09Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-d29eb63d4d5e40e3a3c2b8a250f9ab182023-11-18T00:53:33ZengMDPI AGCells2073-44092023-05-011210143310.3390/cells12101433Regulation of IDO2 by the Aryl Hydrocarbon Receptor (AhR) in Breast CancerSarah Y. Kado0Keith Bein1Alejandro R. Castaneda2Arshia A. Pouraryan3Nicole Garrity4Yasuhiro Ishihara5Andrea Rossi6Thomas Haarmann-Stemmann7Colleen A. Sweeney8Christoph F. A. Vogel9Center for Health and the Environment, University of California, One Shields Avenue, Davis, CA 95616, USACenter for Health and the Environment, University of California, One Shields Avenue, Davis, CA 95616, USACenter for Health and the Environment, University of California, One Shields Avenue, Davis, CA 95616, USACenter for Health and the Environment, University of California, One Shields Avenue, Davis, CA 95616, USACenter for Health and the Environment, University of California, One Shields Avenue, Davis, CA 95616, USAGraduate School of Integrated Arts and Sciences, Hiroshima University, Hiroshima 739-8521, JapanLeibniz Research Institute for Environmental Medicine, 40225 Düsseldorf, GermanyLeibniz Research Institute for Environmental Medicine, 40225 Düsseldorf, GermanyDepartment of Biochemistry & Molecular Medicine, School of Medicine, University of California, Davis, CA 95817, USACenter for Health and the Environment, University of California, One Shields Avenue, Davis, CA 95616, USAIndoleamine 2,3-dioxygenase 2 (IDO2) is a tryptophan-catabolizing enzyme and a homolog of IDO1 with a distinct expression pattern compared with IDO1. In dendritic cells (DCs), IDO activity and the resulting changes in tryptophan level regulate T-cell differentiation and promote immune tolerance. Recent studies indicate that IDO2 exerts an additional, non-enzymatic function and pro-inflammatory activity, which may play an important role in diseases such as autoimmunity and cancer. Here, we investigated the impact of aryl hydrocarbon receptor (AhR) activation by endogenous compounds and environmental pollutants on the expression of IDO2. Treatment with AhR ligands induced IDO2 in MCF-7 wildtype cells but not in CRISPR-cas9 AhR-knockout MCF-7 cells. Promoter analysis with IDO2 reporter constructs revealed that the AhR-dependent induction of IDO2 involves a short-tandem repeat containing four core sequences of a xenobiotic response element (XRE) upstream of the start site of the human <i>ido2</i> gene. The analysis of breast cancer datasets revealed that IDO2 expression increased in breast cancer compared with normal samples. Our findings suggest that the AhR-mediated expression of IDO2 in breast cancer could contribute to a pro-tumorigenic microenvironment in breast cancer.https://www.mdpi.com/2073-4409/12/10/1433AhRbreast cancerIDOIDO2immunityTCDD |
| spellingShingle | Sarah Y. Kado Keith Bein Alejandro R. Castaneda Arshia A. Pouraryan Nicole Garrity Yasuhiro Ishihara Andrea Rossi Thomas Haarmann-Stemmann Colleen A. Sweeney Christoph F. A. Vogel Regulation of IDO2 by the Aryl Hydrocarbon Receptor (AhR) in Breast Cancer Cells AhR breast cancer IDO IDO2 immunity TCDD |
| title | Regulation of IDO2 by the Aryl Hydrocarbon Receptor (AhR) in Breast Cancer |
| title_full | Regulation of IDO2 by the Aryl Hydrocarbon Receptor (AhR) in Breast Cancer |
| title_fullStr | Regulation of IDO2 by the Aryl Hydrocarbon Receptor (AhR) in Breast Cancer |
| title_full_unstemmed | Regulation of IDO2 by the Aryl Hydrocarbon Receptor (AhR) in Breast Cancer |
| title_short | Regulation of IDO2 by the Aryl Hydrocarbon Receptor (AhR) in Breast Cancer |
| title_sort | regulation of ido2 by the aryl hydrocarbon receptor ahr in breast cancer |
| topic | AhR breast cancer IDO IDO2 immunity TCDD |
| url | https://www.mdpi.com/2073-4409/12/10/1433 |
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