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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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Abstract

Sex difference in the incidence of thyroid cancer with predominance of the disease in women is well known, whereas the underlying mechanism remains obscure. Research performed during the last four decades points out that sex steroids may underlie this bias in thyroid cancer incidence. This review attempts to compile the available information in the area. The authors have taken care to include all relevant publications. If any of the important reports is not included, it is inadvertent and not intentional. A series of reports from our laboratory have established that testosterone stimulates the proliferation and growth of normal thyroid gland in rats of either sex, whereas estradiol has a specific stimulatory effect in females and an inhibitory effect in males. Early experimental studies in rats revealed that sex steroids may promote thyroid tumorigenesis;we have shown that testosterone may specifically promote malignancy. We have also shown the stimulatory effect of testosterone and estradiol in human thyroid cancer cell lines NPA-87-1 and WRO-82-1. In a recent paper we reported a positive correlation between AR ligand-binding activity and its protein expression level; AR mRNA expression had a positive correlation with its transcription factors Sp1 and a negative correlation with p53, its repressor in papillary thyroid carcinoma (PTC) or follicular adenoma (FTA) tissues of women. There was inconsistency between expression levels of AR mRNA and its protein, which was influenced by the expression level of the microRNA (miR)-124a. From our in vitro experiments using a human PTC cell line (NPA-87-1) transfected with either miR-124a or anti-miR-124a in the light of our findings from human thyroid tumor tissues, we have shown for the first time that miR-124a is a potent inhibitor of AR expression, and its expression pattern may determine the mitogenic effect of testosterone on thyroid cancer.

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Acknowledgments

This study was supported by the Government of India, Department of Biotechnology (DBT) in the form of a major research project (BT/PR4841/Med/12/187/2004) to Prof. M. Michael Aruldhas, and financial support from University Grants Commission under the Special Assistance Programme and the Department of Science and Technology under FIST Programme is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Endocrinology, Dr. ALM. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600113, TN, India

    Jone A. Stanley (Doctoral student), Ramalingam Neelamohan (Doctoral Students), Esakky Suthagar (Doctoral Students), Kannan Annapoorna (Doctoral Students), Sridharan Sharmila (Doctoral Students), Narasimhan Srinivasan (Professor) & Michael M. Aruldhas (Professor)

  2. Department Integrative Biosciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, 77843, USA

    Jone A. Stanley (Post Doctoral Fellow) & Sakhila K. Banu (Clinical Assistant Professor)

  3. Department of Endocrine Surgery, Madras Medical College, Chennai, 600003, TN, India

    Jayaraman Jayakumar (Post Graduate Student in Medicine) & Maharajan Chandrasekaran (Professor)

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  1. Jone A. Stanley
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Correspondence to Michael M. Aruldhas .

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  1. Computational Biology & Bioinformatics, University of Kerala, Kariavattom, Trivandrum, Kerala, India

    Perumana R. Sudhakaran

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Stanley, J.A. et al. (2014). Androgen Receptor Expression in Human Thyroid Cancer Tissues: A Potential Mechanism Underlying the Gender Bias in the Incidence of Thyroid Cancers. In: R. Sudhakaran, P. (eds) Perspectives in Cancer Prevention-Translational Cancer Research. Springer, New Delhi. https://doi.org/10.1007/978-81-322-1533-2_10

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