Studies on estradiol dependent transcriptional regulation of human Sodium Iodide Symporter gene in mammary glands

Abstract

Sodium Iodide Symporter (NIS) is a transmembrane protein, which is expressed in thyroid, mammary gland (mg), stomach, and salivary gland. NIS’s transcriptional regulation in terms of cis-and trans-acting elements in thyroid gland is widely studied. However, despite identification of NIS and studies on its hormonal regulation in mammary gland, cis-and trans-acting elements controlling the mgNIS gene in this tissue are not identified yet. From in vivo experiments, it was learned that estrogen has an up regulatory effect on mgNIS transcriptional regulation. In this study, it was shown that in vitro, estrogen (even in pharmacological concentrations) was not able to induce mgNIS in estrogen receptor positive (ER(+)) MCF-7 breast carcinoma cells, and it had no additive effect on retinoic acid (RA) in NIS up regulation when it was administered in physiological concentrations. In ER (-) MDA-MB-231 breast cancarcinoma cells, ERα might be insufficient to induce mgNIS transcription inspite of the fact that ERα was able to transactivate ERE elements. Interestingly, our study indicates that tamoxifen antagonist of ER, together with estrogen induces mgNIS transcription in MCF-7 cell lines in the absence of RA. This study clearly shows the presence of a yet unidentified link between mgNIS regulation and estrogen responsive mechanisms. Bearing in mind that tamoxifen is a powerful substance in treatment of ER(+) breast cancers, and that radioactive iodide is used in thyroid cancer diagnosis and treatment. This weak induction of mgNIS expression in response to tamoxifen may also have interesting novel applications in fight against breast cancer.