BRAFV600E and RET/PTC promote proliferation and migration of papillary thyroid carcinoma cells in vitro by regulating nuclear factor-ºB

Abstract

Background: Papillary thyroid carcinoma (PTC) is associated with mutations of BRAFV600E and RET/PTC and high levels of expression of nuclear factor-ºB (NF-ºB). However, few studies have focused on the association between NF-ºB expression and mutations in BRAFV600E and RET/PTC, especially regarding PTC cell proliferation and migration. The aim of this in vitro study was to investigate the effect of BRAFV600E or RET/PTC on NF-ºB expression, cell proliferation and cell migration in four established PTC cell lines. Material/Methods: Four cell lines included TPC-1 (BRAFWT/WT), BCPAP (BRAFV600E/V600E), PCCL3, and PTC3-5 (RET/PTC), were grown in culture in vitro with or without suppression of NF-ºB 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-kB protein, including phosphorylated p100/52, phosphorylated p65, phosphorylated IKKα/β, phosphorylated IºBα, 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-ºB reduced NF-kB 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: BRAFV600E and RET/PTC and the expression of NF-ºB promote the proliferation and migration of papillary thyroid carcinoma cells in vitro.