Effect of sodium/iodide symporter (NIS)-mediated radioiodine therapy on estrogen receptor-negative breast cancer

Yao,Chen; Pan,Yi; Li,Yongxin; Xu,Xiangdong; Lin,Ying; Wang,Wenjian; Wang,Shenming

doi:10.3892/or.2015.3946

Effect of sodium/iodide symporter (NIS)-mediated radioiodine therapy on estrogen receptor-negative breast cancer

Authors:
- Chen Yao
- Yi Pan
- Yongxin Li
- Xiangdong Xu
- Ying Lin
- Wenjian Wang
- Shenming Wang
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Affiliations: Department of Vascular, Thyroid and Breast Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China, Southern Medical University, Guangzhou, Guangdong 510080, P.R. China, Laboratory of the Department of Surgery, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China
Published online on: May 5, 2015 https://doi.org/10.3892/or.2015.3946
Pages: 59-66

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Abstract

Since the sodium/iodide symporter (NIS) stimulates the iodine uptake in normal lactating breast, our study aimed to study the effect of NIS-mediated radioiodide therapy on ER-negative breast cancers. A recombinant lentivirus plasmid encoding the human NIS (hNIS) gene and firefly luciferase (Fluc) was constructed. MDA-MB-231 cells were transfected with the recombinant lentivirus, and the hNIS gene expression was identified by western blot analysis and real-time PCR. Tissue-specific expression of the NIS gene was confirmed by immunohistochemical (IHC) staining. Functional NIS activity in the MDA-hNIS cells was confirmed by the uptake of 131I and cytotoxicity assays. The relative expression level of hNIS mRNA exhibited a 10-fold higher expression in the MDA-hNIS cells compared with the level in the control cells without the endogenous NIS gene. Abundant expression of hNIS protein was noted in the cell membrane compared to the cytoplasm which confirmed the efficient expression of the functional hNIS gene. Iodine uptake into the MDA-hNIS cells was rapid, reaching a maximum after 15 min, followed by a decline. Exposure of the MDA-hNIS cells with 131I resulted in a time‑dependent reduction in colony formation compared with the survival of the control (MDA) cells. Our results confirmed that NIS overexpression enhances the sensitivity of ER-negative breast cancer cells to radioiodide therapy.

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