期刊
JOURNAL OF SURGICAL RESEARCH
卷 182, 期 1, 页码 85-93出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.jss.2012.08.053
关键词
Papillary thyroid cancer; BRAF (V600E) mutation; Radioactive iodine; Radioactive iodine resistance; Thyroid-stimulating hormone; Sodium-iodine symporter
类别
资金
- Clinical and Translational Science Center at Weill Cornell Medical College [TL1RR024998]
- Dancers Care Foundation
Background: The BRAF(V600E) mutation is present in 62% of radioactive iodine-resistant thyroid tumors and is associated with downregulation of the sodium-iodide symporter (NIS) and thyroid stimulating hormone receptor (TSHr). We sought to evaluate the combined effect of BRAF inhibition and TSH supplementation on I-131 uptake of BRAF(V600E)-mutant human thyroid cancer cells. Materials and methods: WRO cells (a BRAF(V600E)-mutant follicular-derived papillary thyroid carcinoma cell line) were transfected with small interfering RNA targeting BRAF for 72 h in a physiological TSH environment. NIS and TSHr expression were then evaluated at three levels: gene expression, protein levels, and I-131 uptake. These three main outcomes were then reassessed in TSH-depleted media and media supplemented with supratherapeutic concentrations of TSH. Results: NIS gene expression increased 5.5-fold 36 h after transfection (P = 0.01), and TSHr gene expression increased 2.8-fold at 24 h (P = 0.02). NIS and TSHr protein levels were similarly increased 48 and 24 h after transfection, respectively. Seventy-two hours after BRAF inhibition, I-131 uptake was unchanged in TSH-depleted media, increased by 7.5-fold (P < 0.01) in physiological TSH media, and increased by 9.1-fold (P < 0.01) in supratherapeutic TSH media. Conclusions: The combined strategy of BRAF inhibition and TSH supplementation results in greater I-131 uptake than when either technique is used alone. This represents a simple and feasible approach that may improve outcomes in patients with radioactive iodine-resistant thyroid carcinomas for which current treatment algorithms are ineffective. (C) 2013 Elsevier Inc. All rights reserved.
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