Bisphenol A (BPA), a ubiquitous endocrine‐disrupting chemical, alters the function of endocrine system and enhances the susceptibility to tumorigenesis in several hormone‐dependent tumours as thyroid carcinoma. About 50% of papillary thyroid cancers (PTC), the most common type of thyroid malignancy, harbours the BRAF^V600E mutation. This study aimed to investigate a potential combined effect of BPA exposure and BRAF^V600E mutation on epithelial‐mesenchymal transition (EMT) in PTC. Firstly, the level of BPA in plasma, the evaluation of BRAF^V600E mutation and the level of EMT‐related proteins in PTC samples were individually determined. Additionally, the migration, invasion, colony formation capacity and the expression of EMT‐related proteins after exposure to BPA were precisely analysed in vitro thyroid cells genetically modified by the introduction of BRAF^V600E mutation. Moreover, ERK‐Cox2 signalling pathway was also introduced to explore the possible mechanism in PTC development. As expected, whether the clinical investigation or cultured thyroid cells demonstrated that BPA at a concentration compatible with human exposed levels (10^‐7 M) synergized with the BRAF^V600E mutation promoted EMT via the activation of ERK‐Cox2 signalling pathway. Our findings offer some evidence that BPA as an environmental risk factor can facilitate the progression of PTC harbouring BRAF^V600E mutation.

中文翻译：

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人体暴露水平的双酚 A 可促进携带 BRAFV600E 突变的甲状腺乳头状癌的上皮-间质转化

双酚 A (BPA) 是一种普遍存在的内分泌干扰化学物质，可改变内分泌系统的功能，并增强多种激素依赖性肿瘤（如甲状腺癌）的易感性。大约 50% 的甲状腺乳头状癌 (PTC) 是最常见的甲状腺恶性肿瘤，具有BRAF ^V600E突变。本研究旨在调查 BPA 暴露和BRAF ^V600E突变对 PTC 上皮间质转化 (EMT)的潜在联合影响。一、血浆中BPA的含量，BRAF ^V600E的评价PTC 样本中的突变和 EMT 相关蛋白的水平是单独确定的。此外，在通过引入BRAF ^V600E突变进行基因修饰的体外甲状腺细胞中，精确分析了暴露于 BPA 后的迁移、侵袭、集落形成能力和 EMT 相关蛋白的表达。此外，还引入了 ERK-Cox2 信号通路来探索 PTC 发展的可能机制。正如预期的那样，临床研究或培养的甲状腺细胞是否表明与人类暴露水平（10 ^‐7  M）兼容的浓度的 BPA与BRAF ^V600E协同作用突变通过激活 ERK-Cox2 信号通路促进 EMT。我们的研究结果提供了一些证据，表明 BPA 作为环境风险因素可以促进携带BRAF ^V600E突变的 PTC 的进展。