BRAF(V600E) and RET/PTC Promote Proliferation and Migration of Papillary Thyroid Carcinoma Cells In Vitro by Regulating Nuclear Factor-κB

BACKGROUND: Papillary thyroid carcinoma (PTC) is associated with mutations of BRAF(V600E) and RET/PTC and high levels of expression of nuclear factor-κB (NF-κB). However, few studies have focused on the association between NF-κB expression and mutations in BRAF(V600E) and RET/PTC, especially regarding PTC cell proliferation and migration. The aim of this in vitro study was to investigate the effect of BRAF(V600E) or RET/PTC on NF-κB expression, cell proliferation and cell migration in four established PTC cell lines. MATERIAL/METHODS: Four cell lines included TPC-1 (BRAF(WT/WT)), BCPAP (BRAF(V600E/V600E)), PCCL3, and PTC3-5 (RET/PTC), were grown in culture in vitro with or without suppression of NF-κB using pyrrolidine dithiocarbamate (PDTC), and cell proliferation, and cell migration were evaluated. RESULTS: Expression of the BRAF gene was increased in the BCPAP cell line when compared with the TPC-1 cells. Expression of the RET gene was increased in the PTC3-5 cell line when compared with the PCCL3 cells. In the BCPAP and PTC3-5 cell lines, the relative expression of NF-κB protein, including phosphorylated p100/52, phosphorylated p65, phosphorylated IKKα/β, phosphorylated IκBα, and p65 nuclear translocation were increased compared with the TPC-1 and PCCL3 cells. Proliferation and migration of BCPAP and PTC3-5 cells were increased compared with the TPC-1 and PCCL3 cells. Suppression of NF-κB reduced NF-κB protein expression and inhibited the proliferation of cells in the TPC-1, BCPAP, PCCL3 and PTC3-5 cell lines, and migration of the BCPAP and PTC3-5 cells. CONCLUSIONS: BRAF(V600E) and RET/PTC and the expression of NF-κB promote the proliferation and migration of papillary thyroid carcinoma cells in vitro.