Bisphenol A at a human exposed level can promote epithelial-mesenchymal transition in papillary thyroid carcinoma harbouring BRAF(V600E) mutation.

Bisphenol A at a human exposed level can promote epithelial-mesenchymal transition in papillary thyroid carcinoma harbouring BRAF(V600E) mutation.
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人体暴露水平的双酚 A 可以促进携带 BRAF(V600E) 突变的甲状腺乳头状癌的上皮间质转化。

DOI:
10.1111/jcmm.16279
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发表时间:
2021-03
影响因子:
5.3
通讯作者:
Lu X
Lu X
中科院分区:
医学2区
文献类型:
--
作者:
Li L;Li H;Zhang J;Gao X;Jin H;Liu R;Zhang Z;Zhang X;Wang X;Qu P;Zhao Y;Lu X

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双酚A(BPA)是一种普遍存在的内分泌干扰物,可改变内分泌系统的功能,并增强甲状腺癌等几种激素依赖性肿瘤的肿瘤发生易感性。大约50%的甲状腺乳头状癌(PTC)是最常见的甲状腺恶性肿瘤类型,具有BRAF V600 E突变。本研究旨在研究BPA暴露和BRAF V600 E突变对PTC中上皮-间质转化(EMT)的潜在联合作用。首先,分别测定血浆中BPA的水平、BRAFV 600 E突变的评价和PTC样本中EMT相关蛋白的水平。此外,在通过引入BRAF V600 E突变进行遗传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,还介绍了ERK‐ Cox 2信号通路,以探讨PTC发生的可能机制。正如预期的那样,无论是临床研究还是培养的甲状腺细胞都证明,与人体暴露水平(10 - 7 M)相容的BPA浓度与BRAF V600 E突变协同作用,通过激活ERK‐ Cox 2信号通路促进EMT。我们的研究结果提供了一些证据表明,BPA作为一种环境危险因素,可以促进携带BRAF V600 E突变的PTC的进展。
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 BRAFV600E 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.
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