title: Iodine regulates G2/M progression induced by CCL21/CCR7 interaction in primary cultures of papillary thyroid cancer cells with RET/PTC expression.
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.
authors: Department of Pathology, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China.
authors: You-Yuan
authors: YY
authors: Zhang
authors: Department of Pathology, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China.
authors: Ze-Bing
authors: ZB
authors: Liu
authors: Department of Pathology, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China.
authors: Xuan-Guang
authors: XG
authors: Ye
authors: Department of Pathology, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China.
authors: Wei-Min
authors: WM
authors: Ren
mesh_terms: D000328:Adult; D016203:CDC2 Protein Kinase; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002291:Carcinoma, Papillary; D002455:Cell Division; D049109:Cell Proliferation; D054421:Chemokine CCL21 / Q000378:metabolism*; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D019925:Cyclin A / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D005260:Female; D016195:G2 Phase; D015321:Gene Rearrangement; D006801:Humans; D007455:Iodine / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D060066:Protein Interaction Maps; D011519:Proto-Oncogenes; D054400:Receptors, CCR7 / Q000378:metabolism*; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: C515478:CCL21 protein, human; C515370:CCR7 protein, human; D054421:Chemokine CCL21; D019925:Cyclin A; D019926:Cyclin B; D054400:Receptors, CCR7; D007455:Iodine; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases