Aberrant Expression of Androgen Receptor Associated with High Cancer Risk and Extrathyroidal Extension in Papillary Thyroid Carcinoma

• Main Authors: Chen-Kai Chou, Shun-Yu Chi, Fong-Fu Chou, Shun-Chen Huang, Jia-He Wang, Chueh-Chen Chen, Hong-Yo Kang
• Format: Article
• Language: English
• Published: MDPI AG 2020-04-01
• Series: Cancers
• Subjects: papillary thyroid carcinoma; androgen receptor; tumorigenesis; sex difference; epithelial-mesenchymal transition
• Online Access: https://www.mdpi.com/2072-6694/12/5/1109

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.