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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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.
