Iodine regulates G2/M progression induced by CCL21/CCR7 interaction in primary cultures of papillary thyroid cancer cells with RET/PTC expression

Zhang,You‑Yuan; Liu,Ze‑Bing; Ye,Xuan‑Guang; Ren,Wei‑Min

doi:10.3892/mmr.2016.5686

Iodine regulates G2/M progression induced by CCL21/CCR7 interaction in primary cultures of papillary thyroid cancer cells with RET/PTC expression

Authors:
- You‑Yuan Zhang
- Ze‑Bing Liu
- Xuan‑Guang Ye
- Wei‑Min Ren
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Affiliations: Department of Pathology, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China
Published online on: August 29, 2016 https://doi.org/10.3892/mmr.2016.5686
Pages: 3941-3946

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Abstract

Treatment with high iodine concentrations can delay oncogenic activation effects, reduce cell growth and return thyroid-specific gene and protein expression levels to normal. During rearranged during transfection (RET)/papillary thyroid carcinoma (PTC) 3 activation, excess iodine can act as a protective agent in thyroid follicular cells. The chemokine receptor CCR7 serves a critical role in lymphocyte trafficking into and within lymph nodes, the preferential metastatic site for PTC. However, the potential associations between chemokine (C‑C motif) ligand 21 (CCL21)/C‑C chemokine receptor type 7 (CCR7) interaction and iodine concentrations in primary cultures of PTC with RET/PTC expression remain unclear. Proliferation assays of primary cultures of PTC cells with RET/PTC1 and RET/PTC3 expression indicated that CCR7 activation by its specific ligand, CCL21, was associated with significantly increased cell proliferation. Flow cytometry data indicated that CCL21/CCR7 interaction significantly increased the fraction of cells in the G2/M phase of the cell cycle. Western blotting indicated that CCL21/CCR7 interaction significantly upregulated cyclin A, cyclin B1 and cyclin‑dependent kinase 1 (CDK1) expression. Western blotting determined that CCL21/CCR7 interaction significantly enhanced the levels of phosphorylated extracellular signal‑regulated kinase (P‑ERK). Co-immunoprecipitation confirmed that there was interaction between P‑ERK and cyclin A, cyclin B1 or CDK1, particularly in the presence of CCL21. Sodium iodide (NaI, 10-5 M) significantly abolished the effects of exogenous CCL21. These results suggest that CCL21/CCR7 interaction contributes to G2/M progression of RET/PTC‑expressing cells via the ERK pathway in association with 10‑5 M NaI.

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