G protein-coupled estrogen receptor deficiency accelerates liver tumorigenesis by enhancing inflammation and fibrosis
Copyright © 2016 Elsevier Ireland Ltd. All rights reserved..
G protein-coupled estrogen receptor (GPER) is a novel estrogen-binding receptor involved in many pathological conditions, including cancer. In this study, we investigated the effect of GPER on hepatocellular carcinoma (HCC). Our data show GPER knockout in a diethylnitrosamine (DEN)-induced mouse tumor model significantly accelerated liver tumorigenesis, accompanied by enhanced immune cell infiltration, fibrosis, and the production of inflammatory factors, such as interleukin-6 (IL-6). We further delineated the function of GPER in macrophages and hepatic stellate cells (HSCs). Treatment with the selective GPER agonist, G-1, decreased the expression of IL-6 in bone marrow-derived macrophages, which was abrogated upon deficiency of GPER. In a HSC line (LX2), G-1 treatment downregulated the expression of α-smooth muscle actin. In addition, both GPER mRNA and protein levels were significantly lower in HCC compared with matched non-tumor tissues. However, modulating GPER expression did not affect the viability and proliferation of hepatoma cells in vitro. Together our results indicate that GPER protects against HCC tumorigenesis through regulating inflammatory responses rather than directly acting on tumor cells. Therefore, GPER activation may be a potential strategy for prevention and treatment of HCC.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:382 |
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| Enthalten in: |
Cancer letters - 382(2016), 2 vom: 28. Nov., Seite 195-202 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wei, Tao [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.07.2017 Date Revised 26.11.2019 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.canlet.2016.08.012 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM264046501 |
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| 100 | 1 | |a Wei, Tao |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a G protein-coupled estrogen receptor deficiency accelerates liver tumorigenesis by enhancing inflammation and fibrosis |
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| 500 | |a Date Revised 26.11.2019 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2016 Elsevier Ireland Ltd. All rights reserved. | ||
| 520 | |a G protein-coupled estrogen receptor (GPER) is a novel estrogen-binding receptor involved in many pathological conditions, including cancer. In this study, we investigated the effect of GPER on hepatocellular carcinoma (HCC). Our data show GPER knockout in a diethylnitrosamine (DEN)-induced mouse tumor model significantly accelerated liver tumorigenesis, accompanied by enhanced immune cell infiltration, fibrosis, and the production of inflammatory factors, such as interleukin-6 (IL-6). We further delineated the function of GPER in macrophages and hepatic stellate cells (HSCs). Treatment with the selective GPER agonist, G-1, decreased the expression of IL-6 in bone marrow-derived macrophages, which was abrogated upon deficiency of GPER. In a HSC line (LX2), G-1 treatment downregulated the expression of α-smooth muscle actin. In addition, both GPER mRNA and protein levels were significantly lower in HCC compared with matched non-tumor tissues. However, modulating GPER expression did not affect the viability and proliferation of hepatoma cells in vitro. Together our results indicate that GPER protects against HCC tumorigenesis through regulating inflammatory responses rather than directly acting on tumor cells. Therefore, GPER activation may be a potential strategy for prevention and treatment of HCC | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a GPER | |
| 650 | 4 | |a Hepatocellular carcinoma | |
| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a Interleukin-6 | |
| 650 | 7 | |a GPER1 protein, human |2 NLM | |
| 650 | 7 | |a GPER1 protein, mouse |2 NLM | |
| 650 | 7 | |a Inflammation Mediators |2 NLM | |
| 650 | 7 | |a Interleukin-6 |2 NLM | |
| 650 | 7 | |a Receptors, Estrogen |2 NLM | |
| 650 | 7 | |a Receptors, G-Protein-Coupled |2 NLM | |
| 650 | 7 | |a interleukin-6, mouse |2 NLM | |
| 650 | 7 | |a Diethylnitrosamine |2 NLM | |
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| 700 | 1 | |a Chen, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Wen, Liang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Jiaqi |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Bryan Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Yue |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Xinhua |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Bai, Xueli |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Tingbo |e verfasserin |4 aut | |
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