Graduate Institution of Clinical Medical Science, Graduate Institute of BioMedical Sciences, Department of Pharmacy, China Medical University, Taichung, Taiwan.
Sex Hormone Research Center, Department of Obstetrics and Gynecology, Department of Pathology, Research Center for Tumor Medical Science, China Medical University/Hospital, Taichung, Taiwan.
J Cell Mol Med. 2018 Jan;22(1):46-56. doi: 10.1111/jcmm.13291. Epub 2017 Aug 7.
The androgen receptor (AR) poly-glutamine polymorphism (AR-Q) was reported to play role in endometrial cancer (EMCA) development, yet controversial. Environmental factors interact with genetic variation have been reported in EMCA. Aerosol toxins, polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP), are EMCA facilitators. This report examined the interplay between AR-Qs and BaP in EMCA. During analysing patient AR-Q polymorphism and Aryl hydrocarbon Receptor (AhR) expressions, we found overall survival (OS) benefit is ascending with AR-Q lengths (5-year OS of 61.3% in Q length <20 and 88% in Q length >23). And AhR is higher expressed in short AR-Q tumour compared to that in long AR-Q patient. In vitro study found androgen-response element (ARE) activity descends with AR-Qs length (Q13 > Q25 > Q35), whereas BaP suppresses ARE activities in EMCA cells. Furthermore, AR-Q13 (but not AR-Q25, or -35) enhances BaP-induced dioxin-responsive element (DRE) activity. Lastly, AR-Q13 exerts higher colony-forming capacity than other AR-Qs, and knock-down AhR abolished AR-Q13-mediated colony numbers. This study demonstrated a possible interaction of gene (AR-Q polymorphism) and environmental toxins (e.g. BaP) to affect cancer progression. A large-scale epidemiology and public health survey on the interaction of environmental toxin and AR poly-Q in EMCA is suggested.
雄激素受体（AR）多聚谷氨酰胺多态性（AR-Q）被报道在子宫内膜癌（EMCA）的发展中起作用，但存在争议。环境因素与遗传变异的相互作用已在 EMCA 中报道。气溶胶毒素、多环芳烃苯并[a]芘（BaP）是 EMCA 的促进剂。本报告研究了 AR-Q 与 BaP 之间在 EMCA 中的相互作用。在分析患者 AR-Q 多态性和芳烃受体（AhR）表达时，我们发现总体生存率（OS）随着 AR-Q 长度的增加而上升（Q 长度<20 的 5 年 OS 为 61.3%，Q 长度>23 的为 88%）。并且 AhR 在短 AR-Q 肿瘤中的表达高于长 AR-Q 患者。体外研究发现雄激素反应元件（ARE）的活性随着 AR-Qs 长度的增加而下降（Q13 > Q25 > Q35），而 BaP 抑制 EMCA 细胞中的 ARE 活性。此外，AR-Q13（而不是 AR-Q25 或 -35）增强了 BaP 诱导的二恶英反应元件（DRE）的活性。最后，AR-Q13 比其他 AR-Qs 具有更高的集落形成能力，敲低 AhR 则消除了 AR-Q13 介导的集落数量。本研究表明基因（AR-Q 多态性）和环境毒素（如 BaP）之间的相互作用可能影响癌症的进展。建议对 EMCA 中环境毒素和 AR 多聚-Q 相互作用进行大规模的流行病学和公共卫生调查。
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