Studies on estradiol dependent transcriptional regulation of human Sodium Iodide Symporter gene in mammary glands
Author
Gülbağcı, Neriman Tuba
Advisor
Tazebay, Uygar H.
Date
2002Publisher
Bilkent University
Language
English
Type
ThesisItem Usage Stats
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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.