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FoxP3 in papillary thyroid carcinoma induces NIS repression through activation of the TGF-β1/Smad signaling pathway

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Tumor Biology

Abstract

Forkhead box P3 (FoxP3) expression in papillary thyroid carcinoma (PTC) is associated with resistance to radioiodine treatment. The sodium iodine symporter (NIS) is a plasma membrane glycoprotein, the repression of which may render the tumor refractive to radioiodine therapy. In this study, samples from 90 PTCs as well as 40 normal thyroid tissues were examined for FoxP3 and NIS by immunohistochemistry and real-time PCR. We found that FoxP3 was associated with decreased NIS expression. Lentiviral-mediated FoxP3-overexpressing cells were constructed and real-time PCR and western blotting were performed to evaluate the expression of NIS. Meanwhile, key members of the transforming growth factor-β1 (TGF-β1) pathway were explored by ELISA and immunofluorescence and a neutralizing TGF-β1 antibody was used to block activity. In vitro, FoxP3 overexpression significantly reduced NIS transcript and protein levels and the TGF-β1 pathway was activated. However, treatment with neutralizing TGF-β1 antibody partially abrogated FoxP3-induced NIS repression. These findings suggest that FoxP3 could compromise NIS expression by inducing TGF-β1.

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Acknowledgments

This work was supported by grants from the Innovation Scientists and Technicians Troop Construction Projects of Henan Province (No. 134200510021). The authors appreciate the generous help of the Institute of Clinical Medicine (The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China) in providing the necessary facilities, and Jun Ouyang and Jinfa Li from the endocrinology laboratory of The First Affiliated Hospital of Zhengzhou University.

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Authors and Affiliations

  1. Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, 40 Daxue Road, Zhengzhou, 450052, China

    Siyuan Ma, Qingzhu Wang, Xiaojun Ma, Lina Wu, Feng Guo, Hongfei Ji, Fei Liu, Yanyan Zhao & Guijun Qin

  2. Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

    Siyuan Ma, Qingzhu Wang, Xiaojun Ma, Lina Wu, Feng Guo, Hongfei Ji, Fei Liu, Yanyan Zhao & Guijun Qin

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  1. Siyuan Ma
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  2. Qingzhu Wang
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  9. Guijun Qin
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Correspondence to Guijun Qin.

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Ma, S., Wang, Q., Ma, X. et al. FoxP3 in papillary thyroid carcinoma induces NIS repression through activation of the TGF-β1/Smad signaling pathway. Tumor Biol. 37, 989–998 (2016). https://doi.org/10.1007/s13277-015-3848-6

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  • DOI: https://doi.org/10.1007/s13277-015-3848-6

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