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Establishment of Canine Transitional Cell Carcinoma Cell Lines Harboring BRAF V595E Mutation as a Therapeutic Target

1
Department of Veterinary Biochemistry, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
2
Department of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
3
Department of Veterinary Emergency and Critical Care, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
4
Department of Veterinary Surgery, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Chien-Feng Li and Yow Ling Shiue
Int. J. Mol. Sci. 2021, 22(17), 9151; https://doi.org/10.3390/ijms22179151
Received: 23 July 2021 / Revised: 20 August 2021 / Accepted: 20 August 2021 / Published: 25 August 2021
(This article belongs to the Special Issue Molecular Pathogenesis and Therapeutics in Urothelial Carcinoma)
Transitional cell carcinoma (TCC) is the most common malignant tumor of the canine urinary tract and tends to have a poor prognosis due to its invasive potential. Recent studies have reported that up to 80% of canine urothelial carcinoma has the BRAF V595E mutation, which is homologous to the human V600E mutation. Activating the BRAF mutation is an actionable target for developing effective therapeutic agents inhibiting the BRAF/mitogen-activated protein kinase (MAPK) pathway in canine cancer as well as human cancer. We established novel canine TCC cell lines from two tumor tissues and one metastatic lymph node of canine TCC patients harboring the BRAF V595E mutation. Tumor tissues highly expressed the BRAF mutant and phosphorylated extracellular signal-related kinases (ERK)1/2 proteins. The derived cell lines demonstrated activated MAPK pathways. We also evaluated the cell lines for sensitivity to BRAF inhibitors. Sorafenib, a multiple kinase inhibitor targeting RAF/vascular endothelial growth factor receptor (VEGFR), successfully inhibited the BRAF/MAPK pathway and induced apoptosis. The established canine TCC cell lines responded with greater sensitivity to sorafenib than to vemurafenib, which is known as a specific BRAF inhibitor in human cancer. Our results demonstrated that canine TCC cells showed different responses compared to human cancer with the BRAF V600E mutation. These cell lines would be valuable research materials to develop therapeutic strategies for canine TCC patients. View Full-Text
Keywords: dog; transitional cell carcinoma; canine BRAF V595E; cancer cell line; metastatic lymph node dog; transitional cell carcinoma; canine BRAF V595E; cancer cell line; metastatic lymph node
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MDPI and ACS Style

Jung, H.; Bae, K.; Lee, J.Y.; Kim, J.-H.; Han, H.-J.; Yoon, H.-Y.; Yoon, K.-A. Establishment of Canine Transitional Cell Carcinoma Cell Lines Harboring BRAF V595E Mutation as a Therapeutic Target. Int. J. Mol. Sci. 2021, 22, 9151. https://doi.org/10.3390/ijms22179151

AMA Style

Jung H, Bae K, Lee JY, Kim J-H, Han H-J, Yoon H-Y, Yoon K-A. Establishment of Canine Transitional Cell Carcinoma Cell Lines Harboring BRAF V595E Mutation as a Therapeutic Target. International Journal of Molecular Sciences. 2021; 22(17):9151. https://doi.org/10.3390/ijms22179151

Chicago/Turabian Style

Jung, Hyojik, Kieun Bae, Ja Young Lee, Jung-Hyun Kim, Hyun-Jung Han, Hun-Young Yoon, and Kyong-Ah Yoon. 2021. "Establishment of Canine Transitional Cell Carcinoma Cell Lines Harboring BRAF V595E Mutation as a Therapeutic Target" International Journal of Molecular Sciences 22, no. 17: 9151. https://doi.org/10.3390/ijms22179151

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