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

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.