Endocrine Abstracts

The Na+/I- symporter (NIS) is a plasma membrane glycoprotein that mediates active I- transport in the thyroid follicular cells (the first step in thyroid hormone biosynthesis), and in other tissues, such as lactating mammary gland. NIS is the basis for the effective use of radioiodide in the diagnostic and treatment of thyroid cancer. NIS mutations hae been identified as causes of congenital iodide transport defect (ITD). We have isolated the cDNA that encodes NIS, generated high-affinity anti-NIS Abs, carried out an extensive characterization of NIS at the molecular level, and studied the regulation of NIS in the thyroid and breast. We have analyzed the expression of NIS in a large sample of thyroid cancers and also demonstrated for the first time that NIS is expressed in over 80% of human breast cancers.
Far from lacking NIS expression, as many as 70% of the thyroid cancer samples overexpressed NIS relative to surrounding tissue. Significantly, NIS was mostly localized intracellularly. This pattern of NIS expression is similar to the one we have observed in FRTL-5 cells deprived of TSH, in which NIS is clearly located intracellularly.
NIS activity was demonstrated in vivo in all mammary adenocarcinomas in polyoma T-antigen transgenic mice. A single intravenous dose of 300 μCi 131I resulted in a 40% slower average tumor growth rate after 4 weeks in the experimental mice, as compared to the control group that received no radioiodine. Our findings of NIS expression in mammary adenocarcinomas in transgenic mice and in human breast cancer suggest that radioiodide, as selectively transported via endogenous NIS, represents a novel potential alternative diagnostic and therapeutic modality in breast cancer. Radioiodide may be administered to breast cancer patients whose thyroids are protected by downregulation of thyroid NIS with T3.