BDE-209长期暴露经TR信号通路诱导甲状腺乳头状癌发生发展的机制

甲状腺癌发病机制的研究越来越关注环境污染物，而全球应用最广泛的阻燃剂十溴联苯醚（BDE-209）成为该领域研究的热点。新近报道人血清BDE-209浓度与甲状腺乳头状癌（PTC）发病率升高和肿瘤侵袭性相关。我们研究发现PTC患者血清中BDE-209浓度显著高于对照组，BDE-209对具有BRAF基因突变者PTC癌细胞促增殖和浸润的作用明显强于伴有RET/PTC1基因突变者。同时发现甲状腺激素受体（TR）α和β在此过程中有不同程度下调。为此，本课题将以BDE-209为中心，运用临床流行病学、构建BDE-209染毒动物模型、转染质粒等手段深入探讨BDE-209和PTC的相关性、诱导PTC发生、发展的机制。将为PTC的防治提供新靶点和思路，具有重要理论价值。

The carcinogenesis of environmental pollutant of thyroid carcinoma became a key point. Decabromodi-phenyl ether (BDE-209) is the most widely used flame retardant in the world, which became a hot topic recently. It was reported that the concentration of serum of BDE-209 correlates with the increase incidence and invasiveness of PTC. Our latest study demonstrated that BDE-209 were in a significantly high level in the PTC patients. In vitro study confirmed that BDE-209 could induce the proliferation of both normal human thyroid follicular cell and thyroid carcinoma cells especially in PTC with BRAFV600E mutation. We will probe into the case-control study of the correlation between concentration of BDE-209 in the indoor dust and the serum of the PTC patient and the clinicopathological features of PTC, to explore the possible mechanism of BDE-209 on the development of PTC through TR signal way. This study would provide useful data for exploring the mechanism of PTC and find new target for tumor prevention and clinical target therapy.