We summarize our current knowledge of NIS modulation in normal and cancer thyroid cells, and we propose that several reagents evaluated in clinical trials for other diseases can be used to restore or further increase RAI accumulation in thyroid cancer.
Our findings not only reveal an epigenetic mechanism for BRAF V600E-promoted NIS silencing involving histone deacetylation at critical regulatory regions of the NIS promoter but also provide further support for our previously proposed combination therapy targeting major signaling pathways and histone deacetylase to restore thyroid gene expression for radioiodine treatment of thyroid cancer.
Thyroid iodide accumulation via the sodium/iodide symporter (NIS; SLC5A5) has been the basis for the longtime use of radio-iodide in the diagnosis and treatment of thyroid cancers.
In mouse models of thyroid cancer, selective mitogen-activated protein kinase (MAPK) pathway antagonists increase the expression of the sodium-iodide symporter and uptake of iodine.Their effects in humans are not known.
NIS-mediated iodide uptake in thyroid cells is the basis for targeted radionuclide imaging and treatment of differentiated thyroid carcinomas and their metastases.
Determination of the optimal time for radioiodine therapy in anaplastic thyroid carcinoma using the adenovirus-mediated transfer of sodium iodide symporter gene.
The NIS protein mainly locates in the cytoplasm, which therefore lacks the ability of transporting and absorbing iodine in patients with thyroid carcinoma.
The cotransduction of TTF-1 and Pax-8 gene, with resulting NIS-mediated radioiodine accumulation and TPO and Tg-mediated radioiodine organification and intracellular retention, may lead to effective radioiodine therapy of thyroid carcinoma.
In principle, undifferentiated thyroid cancers as well as nonthyroid cancers can concentrate and, thus, be treated with radioiodine after transfection with the human sodium iodide symporter (hNIS) gene.
The sodium-iodide symporter (NIS), which mediates iodide uptake into thyroid cells, and is the molecular basis of radioiodine imaging and therapy in thyroid cancer, is also expressed in a large portion of breast tumors.
These targets include the proto-oncogenes BRAF and RET, known to be common mutations in thyroid cancer; vascular endothelial growth factor receptor and platelet-derived growth factor receptor, associated with angiogenesis; and the sodium-iodide symporter, with the aim of restoring its expression and hence radioactive iodine uptake.
Our study describes a novel mechanism of NIS repression in thyroid cancer and provides evidence that TGFbeta may play a key role in promoting radioiodide resistance and tumor invasion during PTC progression.
The lack of Na(+)/I(-) symporter (NIS) gene expression in some thyroid cancer patients has been a major hurdle that limits the efficacy of standard radioactive iodide therapy.
TSH stimulation of sodium iodide symporter (NIS) expression in thyroid cancer promotes radioiodine uptake and is required to deliver an effective treatment dose.
Treatment of thyroid carcinoma cells (four papillary and two anaplastic cell lines) with histone deacetylase inhibitors (SAHA or VPA) modestly induced the expression of the NIS gene.
Methylation of thyroid-specific genes, such as those for sodium/iodide symporter and thyroid-stimulating hormone receptor, is also common in thyroid cancer.
The ability of thyroid cells to take up iodide, which enables (131)I radiotherapy for thyroid cancer, is due to the expression of the sodium iodide symporter at their plasma membrane.
Reduced NIS gene expression in thyroid cancer is likely due in part, to impaired trans-activation at the proximal promoter and/or the upstream enhancer.