Aberrant Expression of Androgen Receptor Associated with High Cancer Risk and Extrathyroidal Extension in Papillary Thyroid Carcinoma
Male gender is a risk factor for mortality in patients with papillary thyroid carcinoma (PTC). This study investigated the impact of androgen receptor (<i>AR</i>) gene expression on the clinical features and progression of PTC. The levels of <i>AR</i> mRNA and protein in froz...
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MDPI AG
2020-04-01
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author | Chen-Kai Chou Shun-Yu Chi Fong-Fu Chou Shun-Chen Huang Jia-He Wang Chueh-Chen Chen Hong-Yo Kang |
author_facet | Chen-Kai Chou Shun-Yu Chi Fong-Fu Chou Shun-Chen Huang Jia-He Wang Chueh-Chen Chen Hong-Yo Kang |
author_sort | Chen-Kai Chou |
collection | DOAJ |
description | Male gender is a risk factor for mortality in patients with papillary thyroid carcinoma (PTC). This study investigated the impact of androgen receptor (<i>AR</i>) gene expression on the clinical features and progression of PTC. The levels of <i>AR</i> mRNA and protein in frozen, formalin-fixed, paraffin-embedded tissue samples from PTC and adjacent normal thyroid tissue were assessed by quantitative real-time polymerase chain reaction and immunohistochemical staining, respectively, and the relationships between <i>AR</i> expression and clinical features were analyzed. The thyroid cancer cell lines, BCPAP and TPC-1, were used to evaluate the effects of <i>AR</i> on the regulation of cell migration, and key epithelial–mesenchymal transition (EMT) markers. <i>AR</i> mRNA expression was significantly higher in normal thyroid tissue from men than women. The sex difference in <i>AR</i> mRNA expression diminished during PTC tumorigenesis, as <i>AR</i> mRNA expression levels were lower in PTC than normal thyroid tissues from both men and women. <i>AR</i> mRNA expression was significantly decreased in PTC patients with higher risk and in those with extrathyroidal extension. Overexpression of <i>AR</i> in BCPAP cells decreased cell migration and repressed the EMT process by down-regulating mRNA expression of <i>N-cadherin</i>, <i>Snail1</i>, <i>Snail2</i>, <i>Vimentin</i>, and <i>TWIST1</i> and up-regulating <i>E-cadherin</i> gene expression. These results suggest that suppression of the androgen–<i>AR</i> axis may lead to aggressive tumor behavior in patients with PTC. |
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language | English |
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spelling | doaj.art-7765e1660d7347ee840b6ddd315a739f2023-11-19T23:01:14ZengMDPI AGCancers2072-66942020-04-01125110910.3390/cancers12051109Aberrant Expression of Androgen Receptor Associated with High Cancer Risk and Extrathyroidal Extension in Papillary Thyroid CarcinomaChen-Kai Chou0Shun-Yu Chi1Fong-Fu Chou2Shun-Chen Huang3Jia-He Wang4Chueh-Chen Chen5Hong-Yo Kang6Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung City 83301, TaiwanDepartment of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung City 83301, TaiwanDepartment of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung City 83301, TaiwanDepartment of Pathology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung City 83301, TaiwanDivision of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung City 83301, TaiwanDivision of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung City 83301, TaiwanGraduate Institute of Clinical Medical Sciences, Chang Gung University, Kaohsiung City 83301, TaiwanMale gender is a risk factor for mortality in patients with papillary thyroid carcinoma (PTC). This study investigated the impact of androgen receptor (<i>AR</i>) gene expression on the clinical features and progression of PTC. The levels of <i>AR</i> mRNA and protein in frozen, formalin-fixed, paraffin-embedded tissue samples from PTC and adjacent normal thyroid tissue were assessed by quantitative real-time polymerase chain reaction and immunohistochemical staining, respectively, and the relationships between <i>AR</i> expression and clinical features were analyzed. The thyroid cancer cell lines, BCPAP and TPC-1, were used to evaluate the effects of <i>AR</i> on the regulation of cell migration, and key epithelial–mesenchymal transition (EMT) markers. <i>AR</i> mRNA expression was significantly higher in normal thyroid tissue from men than women. The sex difference in <i>AR</i> mRNA expression diminished during PTC tumorigenesis, as <i>AR</i> mRNA expression levels were lower in PTC than normal thyroid tissues from both men and women. <i>AR</i> mRNA expression was significantly decreased in PTC patients with higher risk and in those with extrathyroidal extension. Overexpression of <i>AR</i> in BCPAP cells decreased cell migration and repressed the EMT process by down-regulating mRNA expression of <i>N-cadherin</i>, <i>Snail1</i>, <i>Snail2</i>, <i>Vimentin</i>, and <i>TWIST1</i> and up-regulating <i>E-cadherin</i> gene expression. These results suggest that suppression of the androgen–<i>AR</i> axis may lead to aggressive tumor behavior in patients with PTC.https://www.mdpi.com/2072-6694/12/5/1109papillary thyroid carcinomaandrogen receptortumorigenesissex differenceepithelial-mesenchymal transition |
spellingShingle | Chen-Kai Chou Shun-Yu Chi Fong-Fu Chou Shun-Chen Huang Jia-He Wang Chueh-Chen Chen Hong-Yo Kang Aberrant Expression of Androgen Receptor Associated with High Cancer Risk and Extrathyroidal Extension in Papillary Thyroid Carcinoma Cancers papillary thyroid carcinoma androgen receptor tumorigenesis sex difference epithelial-mesenchymal transition |
title | Aberrant Expression of Androgen Receptor Associated with High Cancer Risk and Extrathyroidal Extension in Papillary Thyroid Carcinoma |
title_full | Aberrant Expression of Androgen Receptor Associated with High Cancer Risk and Extrathyroidal Extension in Papillary Thyroid Carcinoma |
title_fullStr | Aberrant Expression of Androgen Receptor Associated with High Cancer Risk and Extrathyroidal Extension in Papillary Thyroid Carcinoma |
title_full_unstemmed | Aberrant Expression of Androgen Receptor Associated with High Cancer Risk and Extrathyroidal Extension in Papillary Thyroid Carcinoma |
title_short | Aberrant Expression of Androgen Receptor Associated with High Cancer Risk and Extrathyroidal Extension in Papillary Thyroid Carcinoma |
title_sort | aberrant expression of androgen receptor associated with high cancer risk and extrathyroidal extension in papillary thyroid carcinoma |
topic | papillary thyroid carcinoma androgen receptor tumorigenesis sex difference epithelial-mesenchymal transition |
url | https://www.mdpi.com/2072-6694/12/5/1109 |
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