title: The sodium iodide symporter (NIS): regulation and approaches to targeting for cancer therapeutics.
abstract: Expression of the sodium iodide symporter (NIS) is required for efficient iodide uptake in thyroid and lactating breast. Since most differentiated thyroid cancer expresses NIS, β-emitting radioactive iodide is routinely utilized to target remnant thyroid cancer and metastasis after total thyroidectomy. Stimulation of NIS expression by high levels of thyroid-stimulating hormone is necessary to achieve radioiodide uptake into thyroid cancer that is sufficient for therapy. The majority of breast cancer also expresses NIS, but at a low level insufficient for radioiodine therapy. Retinoic acid is a potent NIS inducer in some breast cancer cells. NIS is also modestly expressed in some non-thyroidal tissues, including salivary glands, lacrimal glands and stomach. Selective induction of iodide uptake is required to target tumors with radioiodide. Iodide uptake in mammalian cells is dependent on the level of NIS gene expression, but also successful translocation of NIS to the cell membrane and correct insertion. The regulatory mechanisms of NIS expression and membrane insertion are regulated by signal transduction pathways that differ by tissue. Differential regulation of NIS confers selective induction of functional NIS in thyroid cancer cells, as well as some breast cancer cells, leading to more efficient radioiodide therapy for thyroid cancer and a new strategy for breast cancer therapy. The potential for systemic radioiodide treatment of a range of other cancers, that do not express endogenous NIS, has been demonstrated in models with tumor-selective introduction of exogenous NIS.
authors: Molecular Endocrinology Laboratory, VA Greater Los Angeles Healthcare System, Departments of Medicine and Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90073, USA. tkogai@ucla.edu
authors: Takahiko
authors: T
authors: Kogai
authors: Gregory A
authors: GA
authors: Brent
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007457:Iodine Radioisotopes / Q000494:pharmacology / Q000627:therapeutic use*; D008954:Models, Biological; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D021381:Protein Transport / Q000187:drug effects; D011877:Radionuclide Imaging; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D027981:Symporters / Q000187:drug effects* / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology; D000099209:Sodium-Iodide Symporters
chemical_list: D007457:Iodine Radioisotopes; D027981:Symporters; D014212:Tretinoin; D000099209:Sodium-Iodide Symporters