These data showed that circulating Tg mRNA is not only a more sensitive marker of residual thyroid tissue or thyroid cancer than sTg, particularly in patients during T4 therapy and with positive antithyroglobulin antibodies, but also was more sensitive than NIS mRNA in all patients.
The transcriptional regulation of the human sodium/iodide symporter (NIS) gene in normal and transformed thyroid cells is a crucial issue in attempting to restore iodide uptake and use radioiodine as a therapeutic treatment of thyroid cancer.
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.
Radioiodine whole body scan (WBS), related to sodium iodide symporter (NIS) function, is widely used to detect recurrence/metastasis in postoperative patients with thyroid cancer.
Aberrant expression of the sodium-iodide symporter (NIS) and the resistance to post-operative radioactive iodide treatment is a crucial cause of higher mortality of some thyroid cancer patients.
NIS has been exploited for over 75 years in ablative radioiodine (RAI) treatment of thyroid cancer, where its ability to transport radioisotopes depends on its localization to the plasma membrane.
In conclusion, our study has uncovered the existence of a miR-146b-3p/PAX8/NIS regulatory circuit that may be exploited therapeutically to modulate thyroid cell differentiation and iodide uptake for improved treatment of advanced thyroid cancer.
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.
These data support further translational studies with <sup>18</sup>F-TFB as NIS gene reporter and imaging biomarker for thyroid cancer and other disease processes that import iodide.
In summary, our results elucidate a pump-independent, protumorigenic role for NIS in thyroid cancer via its cross-talk with PTEN signaling.<b>Significance:</b> A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer is ineffective when transmembrane NIS is not expressed.<i></i>.
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.
Radioactive iodide uptake (RAIU) in thyroid follicular epithelial cells, mediated by the sodium iodide symporter (NIS), is the first rate-limiting step in iodide accumulation which provides a mechanism for effective radioiodide treatment for patients with thyroid cancer.
Qualitative analysis of baseline and stimulated TG, NIS and PDS mRNA showed high sensitivity but low specificity in the prediction of thyroid cancer recurrence or metastases (accuracy under THST = 51%, 43% and 54%, respectively), whereas TPO and TSHR mRNA assays had higher specificity but low sensitivity, with accuracy under THST of 67% and 61%, respectively, that improved when these tests were combined.
Several investigators have shown that gene transfer of NIS into a variety of cell types confers increased radioiodine uptake by up to several hundredfold that of controls in nonthyroid cancers as well as in thyroid cancer.
These studies evaluating the etiological roles of these factors in linking breast and thyroid cancer might also improve our understanding and identify new therapeutic approaches, such as sodium/iodide symporter-mediated radioiodine therapy and thyroid-stimulating hormone receptor antagonists, for breast cancer.
Non-invasive NIS imaging with radioactive iodides and iodide analogs has gained much interest in recent years for evaluation of thyroid cancer and NIS reporter expression.
Sodium/iodide symporter (NIS) is a key protein in iodide transport by thyroid cells and this activity is a prerequisite for effective radioiodide treatment of thyroid cancer.