Iodine regulates G2/M progression induced by CCL21/CCR7 interaction in primary cultures of papillary thyroid cancer cells with RET/PTC expression.
Mol Med Rep
; 14(4): 3941-6, 2016 Oct.
Article
in En
| MEDLINE
| ID: mdl-27574129
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 (CC motif) ligand 21 (CCL21)/CC 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 cyclindependent kinase 1 (CDK1) expression. Western blotting determined that CCL21/CCR7 interaction significantly enhanced the levels of phosphorylated extracellular signalregulated kinase (PERK). Co-immunoprecipitation confirmed that there was interaction between PERK 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/PTCexpressing cells via the ERK pathway in association with 105 M NaI.
Full text:
1
Database:
MEDLINE
Main subject:
Thyroid Gland
/
Thyroid Neoplasms
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Carcinoma
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Cell Division
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G2 Phase
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Chemokine CCL21
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Receptors, CCR7
/
Iodine
Limits:
Adult
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Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
Mol Med Rep
Year:
2016
Type:
Article