The sodium/iodide symporter (NIS): recent frontiers
The Na+/I- symporter (NIS) is an intrinsic plasma membrane glycoprotein that mediates active I- transport in the thyroid follicular cells, the first step in thyroid hormone biosynthesis. Na+/I- symport occurs with a two Na+ per one I- stoichiometry. Endogenous functional expression of NIS in thyroid cancer is the foundation for the single most effective and most side effect-free anti-cancerous targeted radiation therapy available, i.e. radioiodide therapy, which has been successfully used in thyroid cancer for over 60 years. After we cloned the cDNA encoding NIS, we undertook the detailed characterization of the protein and carried out analyses of NIS mutations that cause congenital I- transport defect. These studies have revealed highly significant information on the structural requirements of NIS at certain positions. NIS also mediates active I- transport in other tissues, including salivary glands, gastric mucosa, and lactating mammary gland. In the latter, NIS translocates I- into the milk for thyroid hormone biosynthesis by the nursing newborn. We showed that NIS is expressed in lactating (but not in non-lactating) breast. We then demonstrated that over 80% of human breast cancers express NIS and, more recently, we showed NIS functional expression in breast cancer metastases as well. These findings strongly suggest that NIS-mediated radioiodide treatment may be applicable to breast cancer. In addition, gene transfer experiments carried out by other investigators have proved that NIS can potentially render other cancers susceptible to radioiodide treatment, even if they lack endogenous NIS expression. In conclusion, it is clear that the clinical impact of basic NIS research has extended well beyond the thyroid into areas such as diagnosis and treatment of cancer of the breast and possibly other tissues.