The Sodium/Iodide Symporter (NIS): Characterization, Regulation, and Medical Significance
Orsolya Dohán,
Antonio De la Vieja,
Viktoriya Paroder,
Claudia Riedel,
Mona Artani,
Mia Reed,
Christopher S. Ginter and
Nancy Carrasco
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461
Correspondence: Address all correspondence and requests for reprints to: Nancy Carrasco, M.D., Department of Molecular Pharmacology, Albert Einstein College of Medicine, Forchheimer Building, Room 209, 1300 Morris Park Avenue, Bronx, New York 10461. E-mail: carrasco{at}aecom.yu.edu
The Na+/I– symporter (NIS) is an integral plasma membraneglycoprotein that mediates active I– transport into thethyroid follicular cells, the first step in thyroid hormonebiosynthesis. NIS-mediated thyroidal I– transport fromthe bloodstream to the colloid is a vectorial process made possibleby the selective targeting of NIS to the basolateral membrane.NIS also mediates active I– transport in other tissues,including salivary glands, gastric mucosa, and lactating mammarygland, in which it translocates I– into the milk for thyroidhormone biosynthesis by the nursing newborn. NIS provides thebasis for the effective diagnostic and therapeutic managementof thyroid cancer and its metastases with radioiodide. NIS researchhas proceeded at an astounding pace after the 1996 isolationof the rat NIS cDNA, comprising the elucidation of NIS secondarystructure and topology, biogenesis and posttranslational modifications,transcriptional and posttranscriptional regulation, electrophysiologicalanalysis, isolation of the human NIS cDNA, and determinationof the human NIS genomic organization. Clinically related topicsinclude the analysis of congenital I– transport defect-causingNIS mutations and the role of NIS in thyroid cancer. NIS hasbeen transduced into various kinds of cancer cells to renderthem susceptible to destruction with radioiodide. Most dramatically,the discovery of endogenous NIS expression in more than 80%of human breast cancer samples has raised the possibility thatradioiodide may be a valuable novel tool in breast cancer diagnosisand treatment.
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