Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Nov 8:23:5321-5329.
doi: 10.12659/msm.904928.

BRAFV600E and RET/PTC Promote Proliferation and Migration of Papillary Thyroid Carcinoma Cells In Vitro by Regulating Nuclear Factor-κB

Affiliations

BRAFV600E and RET/PTC Promote Proliferation and Migration of Papillary Thyroid Carcinoma Cells In Vitro by Regulating Nuclear Factor-κB

Dehua Zhou et al. Med Sci Monit. .

Abstract

BACKGROUND Papillary thyroid carcinoma (PTC) is associated with mutations of BRAFV600E 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 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-κB expression, cell proliferation and cell migration in four established PTC cell lines. MATERIAL AND 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-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 IKKa/b, 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 BRAFV600E and RET/PTC and the expression of NF-κB promote the proliferation and migration of papillary thyroid carcinoma cells in vitro.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest statement

The authors declare no conflict of interest. All the authors contributed equally to the study. There was no external funding support. Financial support for the study was from the corresponding author and Zhujiang Hospital, Southern Medical University.

Figures

Figure 1
Figure 1
BRAFV600E and RET/PTC activated NF-κB and pyrrolidine dithiocarbamate (PDTC) suppressed NF-κB. * TPC-1+PDTC(−) vs. BCPAP+PDTC(−) or PCCL3+PDTC(−) vs. PTC3-5+PDTC(−), P<0.05; # TPC-1+PDTC(+) vs. BCPAP +PDTC(+) or PCCL3+PDTC(+) vs. PTC3-5+PDTC(+), P<0.05; @ TPC-1+PDTC(−) vs. TPC-1+PDTC(+) or PCCL3+PDTC(−) vs. PCCL3+PDTC(+), P<0.05; & BCPAP +PDTC(−) vs. BCPAP +PDTC(+) or PTC3-5+PDTC(−) vs. PTC3-5+PDTC(+), P<0.05.
Figure 2
Figure 2
BRAFV600E and RET/PTC promoted thyroid cell proliferation and migration through NF-κB. * TPC-1+PDTC(−) vs. BCPAP+PDTC(−) or PCCL3+PDTC(−) vs. PTC3-5+PDTC(−), P<0.05; # TPC-1+PDTC(+) vs. BCPAP +PDTC(+) or PCCL3+PDTC(+) vs. PTC3-5+PDTC(+), P<0.05; @ TPC-1+PDTC(−) vs. TPC-1+PDTC(+) or PCCL3+PDTC(−) vs. PCCL3+PDTC(+), P<0.05; & BCPAP +PDTC(−) vs. BCPAP +PDTC(+) or PTC3-5+PDTC(−) vs. PTC3-5+PDTC(+), P<0.05.

Similar articles

Cited by

References

    1. Hundahl SA, Fleming ID, Fremgen AM, Menck HR. A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985–1995. Cancer. 1998;83(12):2638–48. - PubMed
    1. Marcy PY, Thariat J, Chevenet C, Lacout A. Jugular vein invasion diagnosis and prognosis in thyroid carcinomas. Pol J Radiol. 2016;81:268–69. - PMC - PubMed
    1. Robinson MJ, Cobb MH. Mitogen-activated protein kinase pathways. Curr Opin Cell Biol. 1997;9:180–86. - PubMed
    1. Kimura ET, Nikiforova MN, Zhu Z, et al. High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Res. 2003;63(7):1454–57. - PubMed
    1. Takahashi M. Structure and expression of the RET transforming gene. IARC Sci Publ. 1988;92(92):189–97. - PubMed

MeSH terms