Biology and clinical application of the NIS gene

The sodium iodide symporter (NIS) is a plasma basolateral membrane protein that actively transports iodide to the thyroid follicular cells as the first step of thyroid hormone biosynthesis. NIS also mediates active iodide transport in other human tissues including the salivary glands, lactating mammary gland and gastric mucosa. NIS expression has been recently reported also in several other human tissues but its physiological role is still unclear. Cloning of the NIS gene and the development of specific NIS antibodies have allowed the characterization of the pathogenic role of NIS in thyroid cancer, thyroid autoimmune diseases, congenital hypothyroidism and other, non-thyroidal human diseases. The possibility to increase its levels of expression or to reinduce its expression in thyroid carcinomas that have lost the ability to take up radioiodine is one of the most promising clinically related fields of research. The recent discovery that more than 80% of human breast carcinomas endogenously express NIS protein has opened a very interesting new area of research into the possibility of using radioiodide in the diagnosis and treatment of breast cancer. In an attempt to make tumor cells susceptible to radioiodide destruction, several types of cancer cells have been transfected with the NIS gene. This has demonstrated the feasibility of the in vitro technique but also raised the problem of the absence of the iodide organification machinery in non-thyroidal cells, which, at the moment, represents the major limit of this strategy.