Endocrine Abstracts

Expression of the sodium iodide symporter (NIS) protein, and correct membrane insertion, is required for efficient iodide uptake in thyroid and lactating breast. Radioactive iodide is routinely utilized to target remnant thyroid and metastasis after total thyroidectomy for thyroid cancer. Stimulation of NIS expression by high levels of TSH, however, is necessary to achieve radioiodide uptake into thyroid cancer sufficient for therapy. The majority of breast cancer also expresses NIS protein, but iodide uptake is low and insufficient for routine radioiodine therapy. Retinoic acid is a potent NIS inducer in some breast cancer, but generally not in thyroid cancer. NIS expression and membrane insertion is regulated by activation of signal transduction pathways that are distinct in thyroid and breast cancer. Spontaneous mutations in kinases leads to stimulation of some of these pathways in cancer. Inhibitors have been used to treat aggressive cancer and, in some cases, these inhibitors induce redifferentiation of the cells and restore iodide uptake. Inhibition of NIS membrane insertion by the pituitary tumor-transforming gene 1 protein-binding factor (PBF) may also play a role in regulating iodide uptake in both thyroid and breast cancer. Differential regulation of NIS in thyroid and breast cancer provides potential targets for more efficient radioiodide therapy in thyroid cancer and new approaches to breast cancer therapy. These approaches may also be relevant to systemic radioiodide treatment of a range of other cancers, which do not express endogenous NIS, but can be treated with tumor-selective introduction of exogenous NIS.