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Hyeon-Gun Jee 1 Article
Thyroid
BRAFV600E Mutation Enhances Estrogen-Induced Metastatic Potential of Thyroid Cancer by Regulating the Expression of Estrogen Receptors
Minjun Kim, Su-jin Kim, Seong Yun Ha, Zhen Xu, Youngjin Han, Hyeon-Gun Jee, Sun Wook Cho, Young Joo Park, Kyu Eun Lee
Endocrinol Metab. 2022;37(6):879-890.   Published online December 26, 2022
DOI: https://doi.org/10.3803/EnM.2022.1563
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  • 2 Web of Science
  • 4 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Cross-talk between mitogen-activated protein kinase and estrogen has been reported; however, the role of BRAFV600E in the estrogen responsiveness of thyroid cancer is unknown. We elucidated the effect of BRAFV600E on the estrogen-induced increase in metastatic potential in thyroid cancer.
Methods
Using a pair of cell lines, human thyroid cell lines which harbor wild type BRAF gene (Nthy/WT) and Nthy/BRAFV600E (Nthy/V600E), the expression of estrogen receptors (ERs) and estrogen-induced metastatic phenotypes were evaluated. Susceptibility to ERα- and ERβ-selective agents was evaluated to confirm differential ER expression. ESR expression was analyzed according to BRAFV600E status and age (≤50 years vs. >50 years) using The Cancer Genome Atlas (TCGA) data.
Results
Estradiol increased the ERα/ERβ expression ratio in Nthy/V600E, whereas the decreased ERα/ERβ expression ratio was found in Nthy/WT. BRAFV600E-mutated cell lines showed a higher E2-induced increase in metastatic potential, including migration, invasion, and anchorage-independent growth compared with Nthy/WT. An ERα antagonist significantly inhibited migration in Nthy/V600E cells, whereas an ERβ agonist was more effective in Nthy/WT. In the BRAFV600E group, ESR1/ESR2 ratio was significantly higher in younger age group (≤50 years) compared with older age group (>50 years) by TCGA data analysis.
Conclusion
Our data show that BRAFV600E mutation plays a crucial role in the estrogen responsiveness of thyroid cancer by regulating ER expression. Therefore, BRAFV600E might be used as a biomarker when deciding future hormone therapies based on estrogen signaling in thyroid cancer patients.

Citations

Citations to this article as recorded by  
  • The importance of protein domain mutations in cancer therapy
    Kiran Kumar Chitluri, Isaac Arnold Emerson
    Heliyon.2024; 10(6): e27655.     CrossRef
  • Three cases of thyroid cancer in transgender female veterans receiving gender-affirming estrogen treatment
    John D. Christensen, Hiba T. Basheer
    Endocrine and Metabolic Science.2024; 15: 100177.     CrossRef
  • Association of DNA Promoter Methylation and BRAF Mutation in Thyroid Cancer
    Farzana Jasmine, Briseis Aschebrook-Kilfoy, Mohammad M. Rahman, Garrett Zaagman, Raymon H. Grogan, Mohammed Kamal, Habibul Ahsan, Muhammad G. Kibriya
    Current Oncology.2023; 30(3): 2978.     CrossRef
  • Editorial: Recent advances in papillary thyroid carcinoma: Progression, treatment and survival predictors
    Erivelto Martinho Volpi, Margarita Carmen Ramirez-Ortega, Jose Federico Carrillo
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
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