Thyroid stimulating hormone increases iodine uptake by thyroid cancer cells during BRAF silencing Journal Article
| Authors: | Kleiman, D. A.; Buitrago, D.; Crowley, M. J.; Beninato, T.; Veach, A. J.; Zanzonico, P. B.; Jin, M.; Fahey, T. J. 3rd; Zarnegar, R. |
| Article Title: | Thyroid stimulating hormone increases iodine uptake by thyroid cancer cells during BRAF silencing |
| Abstract: | Background: The BRAFV600E 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 131I uptake of BRAF V600E-mutant human thyroid cancer cells. Materials and methods: WRO cells (a BRAFV600E-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 131I 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, 131I 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 131I 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. |
| Keywords: | adult; clinical article; controlled study; protein expression; gene mutation; human cell; gene targeting; gene expression; small interfering rna; cancer cell culture; genetic transfection; iodine 131; radioactive iodine; algorithm; cancer cell; thyroid carcinoma; gene silencing; b raf kinase; thyrotropin; sodium iodide symporter; papillary thyroid cancer; thyrotropin receptor; braf (v600e) mutation; radioactive iodine resistance; sodium-iodine symporter; thyroid-stimulating hormone |
| Journal Title: | Journal of Surgical Research |
| Volume: | 182 |
| Issue: | 1 |
| ISSN: | 0022-4804 |
| Publisher: | Academic Press Inc., Elsevier Science |
| Date Published: | 2013-01-01 |
| Start Page: | 85 |
| End Page: | 93 |
| Language: | English |
| DOI: | 10.1016/j.jss.2012.08.053 |
| PROVIDER: | scopus |
| PMCID: | PMC3652238 |
| PUBMED: | 22998776 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 3 June 2013" - "CODEN: JSGRA" - "Source: Scopus" |
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