Androgen receptor expression in human thyroid cancer tissues: A potential mechanism underlying the gender bias in the incidence of thyroid cancers

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• 作者：J.A. Stanley^a ; ^d ; M.M. Aruldhas^a ; ^{aruldhasmm@gmail.com} ; ^{aruldhasmm@unom.ac.in} ; M. Chandrasekaran^c ; R. Neelamohan^a ; E. Suthagar^a ; K. Annapoorna^a ; S. Sharmila^a ; J. Jayakumar^c ; G. Jayaraman^b ; N. Srinivasan^a ; S.K. Banu^d
• 关键词：PTC ; papillary thyroid carcinoma ; FTC ; follicular thyroid carcinoma ; ATC ; anaplastic thyroid cancer ; MTC ; medullary thyroid cancer ; FTA ; follicular thyroid adenoma ; AR ; androgen receptor ; ARE ; androgen response element ; E2 ; estradiol ; ER ; estrogen recepto
• 刊名：The Journal of Steroid Biochemistry and Molecular Biology
• 出版年：2012
• 期刊代码：172_09600760
• 类别：med
• 出版时间：May, 2012
• 卷：130
• 期：1-2
• 页码：105-124
• 文件大小：3655 K

摘要

Gender bias in the incidence of thyroid cancer is well known, however, the underlying mechanism is largely unknown. The current study determines variations in the molecular characteristics of thyroid cancers between men and women. Normal and cancerous thyroid tissues were collected from a total of 125 men and women who underwent surgical thyroidectomy. Testosterone levels in serum and thyroid cancer tissues were elevated in women while it decreased in men compared to respective control groups; whereas, ligand binding activity increased in men and decreased in women. Androgen receptor (AR) mRNA expression increased in a majority of men while it decreased in a majority of women except those with follicular thyroid carcinoma (FTC). In thyroid cancers of women, Pearson's correlation analysis showed a positive correlation of AR mRNA with AR protein, CBP and Sp1, whereas AR mRNA showed a negative correlation with p53. In case of men, AR mRNA showed a positive correlation with AR and cyclin D1 proteins in papillary thyroid carcinoma (PTC); and CBP and Sp1 in follicular thyroid adenoma (FTA), whereas AR mRNA showed a positive correlation with p53. Our study identified for the first time that AR is posttranscriptionally regulated by m>miR-124am> in thyroid cancer tissues. Further, our m>in vitrom> studies with a PTC cell line (NPA-87-1) showed m>miR-124am> as the potent inhibitor of AR that impairs cell proliferation even in the presence of testosterone. Thus, the current study suggests that: (i) the varying pattern of testosterone level and AR status in thyroid tissues of men and women may predispose to the gender specific incidence of thyroid tumors and (ii) m>miR-124am> plays a significant role in determining the AR gene expression pattern and thus, androgen mediated thyroid tumor growth.