|
|||||
|
|
Bisphenol A at a human exposed level can promote epithelial-mesenchymal transition in papillary thyroid carcinoma harbouring BRAFV600E mutation |
|
| Authors: | Liuli Li Hao Li Jun Zhang Xin Gao Hao Jin Renqi Liu Zhen Zhang Xuan Zhang Xichang Wang Peng Qu Yuejiao Zhao Xiaobo Lu |
| Institution: | 1. Department of Toxicology, School of Public health, China Medical University, Shenyang, China
Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (lead), ?Investigation (lead), Software (equal), Validation (equal), Visualization (lead), Writing - original draft (equal), Writing - review & editing (lead);2. Department of Toxicology, School of Public health, China Medical University, Shenyang, China Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), ?Investigation (equal), Validation (equal), Visualization (equal), Writing - original draft (equal);3. Department of Oromaxillofacial–Head and Neck Surgery, Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, China Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), ?Investigation (equal), Methodology (equal), Software (equal), Visualization (equal);4. Department of head and Neck Surgery, Cancer Hospital of China Medical University/Liaoning Cancer Hospital & Institute, Shenyang, China Contribution: ?Investigation (supporting), Methodology (equal), Project administration (equal), Software (equal), Supervision (equal), Validation (equal);5. Jin Zhou Center for Disease Control and Prevention, Jinzhou, China Contribution: Methodology (equal), Project administration (supporting), Resources (equal), Software (equal), Supervision (equal), Validation (equal);6. Jin Zhou Center for Disease Control and Prevention, Jinzhou, China Contribution: ?Investigation (supporting), Methodology (equal), Project administration (equal), Resources (equal), Software (equal), Supervision (equal), Validation (equal);7. Jin Zhou Center for Disease Control and Prevention, Jinzhou, China Contribution: ?Investigation (equal), Methodology (equal), Project administration (supporting), Resources (supporting), Validation (equal), Visualization (equal);8. Department of Toxicology, School of Public health, China Medical University, Shenyang, China Contribution: Data curation (equal), Formal analysis (equal), ?Investigation (equal), Methodology (equal), Software (equal), Validation (equal);9. Department of Toxicology, School of Public health, China Medical University, Shenyang, China;10. Department of Toxicology, School of Public health, China Medical University, Shenyang, China Contribution: Formal analysis (equal), ?Investigation (equal), Methodology (equal), Software (equal);11. Department of head and Neck Surgery, Cancer Hospital of China Medical University/Liaoning Cancer Hospital & Institute, Shenyang, China |
| Abstract: | 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 BRAFV600E mutation. This study aimed to investigate a potential combined effect of BPA exposure and BRAFV600E 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 BRAFV600E 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 BRAFV600E 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 BRAFV600E mutation. |
| Keywords: | Bisphenol A BRAFV600E mutation epithelial-mesenchymal transition ERK-Cox2 Papillary thyroid carcinoma |