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Androgen Receptor (AR)-TLR4 Crosstalk Mediates Gender Disparities in Hepatocellular Carcinoma Incidence and Progression
Background: Androgen receptor (AR) has a role in regulating malignancies and gender disparities in hepatocellular carcinoma (HCC). Recently, TLR4 activation is demonstrated to be required for HCC progression; however, whether and how TLR4 interacts with AR is largely unknown. Methods: The tumorigene...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959060/ https://www.ncbi.nlm.nih.gov/pubmed/31956356 http://dx.doi.org/10.7150/jca.30682 |
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author | Han, Qiuju Yang, Dan Yin, Chunlai Zhang, Jian |
author_facet | Han, Qiuju Yang, Dan Yin, Chunlai Zhang, Jian |
author_sort | Han, Qiuju |
collection | PubMed |
description | Background: Androgen receptor (AR) has a role in regulating malignancies and gender disparities in hepatocellular carcinoma (HCC). Recently, TLR4 activation is demonstrated to be required for HCC progression; however, whether and how TLR4 interacts with AR is largely unknown. Methods: The tumorigenesis was detected in female and male mice induced by DEN/CCL(4,) then TLR4 and AR signals were detected in liver tissues by qPCR and FACS. The proliferation, colony formation and migration of HCC cell treated with TLR4 agonist LPS, or/and androgen DHT were evaluated in vitro. Furthermore, the expression of TLR4 and AR was detected by IHC in tissue microarray of HCC, and correlation of AR and TLR4 was defined. Results: Male mice are more susceptible to develop HCC than female mice. Meanwhile, we found baseline TLR4 levels were higher in male mice than in female mice. AR expression in male mice was increased by treatment with DEN/CCL(4). And, AR was constitutively expressed in human HCC cell lines. Dihydrotestosterone (DHT) stimulated TLR4 expression in both HepG2 and HepG2 2.15 cells, which could be blocked by silencing AR. On the other hand, treatment with LPS stimulated AR expression, but it was blocked by treatment with TLR4 antagonist and in cells deficient for TLR4. DHT treatment exacerbated TLR4-induced cellular proliferation, colony formation, migration, and invasion of HepG2 cells. The positive relationship between AR and TLR4 was confirmed in human HCC samples. Conclusions: DHT-AR-TLR4 signaling enhances the development of HCC cells and facilitates their migration and invasion, demonstrating a mechanism underlying gender disparity in HCC. |
format | Online Article Text |
id | pubmed-6959060 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-69590602020-01-18 Androgen Receptor (AR)-TLR4 Crosstalk Mediates Gender Disparities in Hepatocellular Carcinoma Incidence and Progression Han, Qiuju Yang, Dan Yin, Chunlai Zhang, Jian J Cancer Research Paper Background: Androgen receptor (AR) has a role in regulating malignancies and gender disparities in hepatocellular carcinoma (HCC). Recently, TLR4 activation is demonstrated to be required for HCC progression; however, whether and how TLR4 interacts with AR is largely unknown. Methods: The tumorigenesis was detected in female and male mice induced by DEN/CCL(4,) then TLR4 and AR signals were detected in liver tissues by qPCR and FACS. The proliferation, colony formation and migration of HCC cell treated with TLR4 agonist LPS, or/and androgen DHT were evaluated in vitro. Furthermore, the expression of TLR4 and AR was detected by IHC in tissue microarray of HCC, and correlation of AR and TLR4 was defined. Results: Male mice are more susceptible to develop HCC than female mice. Meanwhile, we found baseline TLR4 levels were higher in male mice than in female mice. AR expression in male mice was increased by treatment with DEN/CCL(4). And, AR was constitutively expressed in human HCC cell lines. Dihydrotestosterone (DHT) stimulated TLR4 expression in both HepG2 and HepG2 2.15 cells, which could be blocked by silencing AR. On the other hand, treatment with LPS stimulated AR expression, but it was blocked by treatment with TLR4 antagonist and in cells deficient for TLR4. DHT treatment exacerbated TLR4-induced cellular proliferation, colony formation, migration, and invasion of HepG2 cells. The positive relationship between AR and TLR4 was confirmed in human HCC samples. Conclusions: DHT-AR-TLR4 signaling enhances the development of HCC cells and facilitates their migration and invasion, demonstrating a mechanism underlying gender disparity in HCC. Ivyspring International Publisher 2020-01-01 /pmc/articles/PMC6959060/ /pubmed/31956356 http://dx.doi.org/10.7150/jca.30682 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Han, Qiuju Yang, Dan Yin, Chunlai Zhang, Jian Androgen Receptor (AR)-TLR4 Crosstalk Mediates Gender Disparities in Hepatocellular Carcinoma Incidence and Progression |
title | Androgen Receptor (AR)-TLR4 Crosstalk Mediates Gender Disparities in Hepatocellular Carcinoma Incidence and Progression |
title_full | Androgen Receptor (AR)-TLR4 Crosstalk Mediates Gender Disparities in Hepatocellular Carcinoma Incidence and Progression |
title_fullStr | Androgen Receptor (AR)-TLR4 Crosstalk Mediates Gender Disparities in Hepatocellular Carcinoma Incidence and Progression |
title_full_unstemmed | Androgen Receptor (AR)-TLR4 Crosstalk Mediates Gender Disparities in Hepatocellular Carcinoma Incidence and Progression |
title_short | Androgen Receptor (AR)-TLR4 Crosstalk Mediates Gender Disparities in Hepatocellular Carcinoma Incidence and Progression |
title_sort | androgen receptor (ar)-tlr4 crosstalk mediates gender disparities in hepatocellular carcinoma incidence and progression |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959060/ https://www.ncbi.nlm.nih.gov/pubmed/31956356 http://dx.doi.org/10.7150/jca.30682 |
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