Iodine regulates G(2)/M progression induced by CCL21/CCR7 interaction in primary cultures of papillary thyroid cancer cells with RET/PTC expression

摘要

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 G(2)/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 G(2)/M progression of RET/PTC-expressing cells via the ERK pathway in association with 10(-5) M NaI.