BRAF V600E Transduction of an SV40-Immortalized Normal Human Thyroid Cell Line Induces Dedifferentiated Thyroid Carcinogenesis in a Mouse Xenograft Model
Open accessAbstract
Background: Despite active studies of the clinical importance of BRAF V600E , suitable research models to investigate the role of this mutation in the etiopathogenesis of human thyroid cancers are limited. Thus, we generated cell lines by transducing the simian virus (SV)-40 immortalized human thyroid cell line Nthy-ori 3-1 (Nthy) with lentiviral vectors expressing either BRAF WT (Nthy/WT) or BRAF V600E . Nthy/WT and Nthy/V600E cells were then xenografted into mice to evaluate the carcinogenic role of BRAF V600E . Methods: Each cell line was subcutaneously injected into NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ mice, and a pathological analysis was performed. The effects of the mutation were further verified by using a BRAF V600E -selective inhibitor (PLX-4032, vemurafenib). The transcriptome was analyzed by RNA sequencing and compared with data from The Cancer Cell Line Encyclopedia and Gene Expression Omnibus. Results: While Nthy/WT was not tumorigenic in vivo , Nthy/V600E formed tumors reaching 2784.343 mm 3 in 4 weeks, on average. A pathological analysis indicated that Nthy/V600E tumors were dedifferentiated thyroid cancer. We found metastases in the lung, liver, and relevant lymph nodes. A transcriptomic analysis revealed 5512 differentially expressed genes (DEGs) between the mutant and wild-type cell lines, and more DEGs were shared with anaplastic thyroid cancer than with papillary thyroid cancer. BRAF V600E activated the cell cycle mainly by regulating G1/S phases. PLX-4032…
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Nthy/BRAFV600E cells gain the capability to form thyroid tumors in vivo, with high metastasis potential and ATC-like transcriptome.
“Nthy/BRAFV600E cells gain the capability to form thyroid tumors in vivo, with high metastasis potential and ATC-like transcriptome44.”
From Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis (2024) · cites this paper as [44]
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Zhang, Z., Wu, Y., Fu, J., Yu, X., Su, Y., Jia, S., Cheng, H., Shen, Y., He, X., Ren, K., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48173-9 · Cited by 14 · see citing works
“Nthy/ BRAF V600E cells gain the capability to form thyroid tumors in vivo, with high metastasis potential and ATC-like transcriptome 44 .”
Background
- Authors
- Kim, M., Kim, S.-J., Xu, Z., Ha, S. Y., Byeon, J. H., Kang, E. J., Shin, S.-H., Yoo, S.-K., Jee, H.-G., Yoon, S. G., Yi, J. W., Bae, J. M., Yu, H. W., Chai, Y. J., Cho, S. W., Choi, J. Y., Lee, K. E., & Han, W.
- Affiliations
- Seoul National University (KR)
- Yonsei University (KR)
- Macrogen (South Korea) (KR)
- Seoul National University Bundang Hospital (KR)
- Kosin University Gospel Hospital (KR)
- Inha University (KR)
- Corresponding author
- Bae, Jeong Mo
- Lee, Kyu Eun
- ORCID
- Venue
- Thyroid
- Publisher
- SAGE Publications
- Published
- 2020-04-01
- Volume
- 30
- Issue
- 4
- Pages
- 487-500
- ISSN
- 1050-7256 (ISSN-L)
- 1557-9077
- OpenAlex
- W3009607961
- Cited by
- 11
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 3 · 2020: 1
- FWCI
- 1.70
- Type
- journal article
- Language
- en
- Open access
- Locations
- Thyroid (publishedVersion)
- PubMed (publishedVersion)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Keywords
- BRAF V600E mutation, thyroid carcinogenesis, lentiviral transduction, xenograft mouse model, vemurafenib, anaplastic thyroid carcinoma, transcriptome, G1/S cell cycle regulation, metastasis, differentially expressed genes
- MeSH terms
- Animals, Cell Line, Humans, Thyroid Gland, Thyroid Neoplasms, Transduction, Genetic, Gene Expression Profiling, Proto-Oncogene Proteins B-raf, Mice, Cell Dedifferentiation, Transcriptome, Carcinogenesis, Heterografts
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