Browsing by Subject "NIS"

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Open Access
The comparative effects of gene modulators on thyroid-specific genes and radioiodine uptake
(Mary Ann Liebert, 2007) Tuncel, M.; Aydın, D.; Yaman, Elif; Tazebay, Uygar H.; Güç, D.; Doğan, A. L.; Taşbasan, B.; Uǧur, Ö.
The aim of this study was to comparatively investigate the effects of 5-azacytidine-C (5-Aza), trichostatin-A (TSA), and all-trans retinoic acid (ATRA) on mRNA expressions of Na/I symporter (NIS), thyroglobulin (Tg), thyroid peroxidase (TPO), and thyroid stimulating hormone receptor (TSH-R), and radioiodine (RAI) uptake in cancer (B-CPAP) and normal (Nthy-ori 3-1) thyroid cell lines. Cell lines were treated with 10 ng/mL of TSA, 5 μM of 5-Aza, and 1 μM of ATRA, according to the MTT (methyl-thiazol-tetrazolium) test results. Additionally, recombinant thyroid stimulating hormone (rTSH) was also applied, with a selected dose of 100 ng/mL. Following the treatment, NIS, Tg, TPO, and TSH-R mRNA levels were detected by real-time-polymerase chain reaction (RT-PCR) and RAI uptakes were measured by using a well counter as the counts/cell number. 5-Aza increased TSH-R mRNA expression in both of the cell lines and decreased TPO, NIS, and Tg mRNA levels in the cancer cell line. In the normal thyroid cell line, 5-Aza increased TPO mRNA levels 2-fold and made no differences in NIS and Tg mRNA levels. TSA treatment repressed NIS and Tg mRNA levels, and made no differences on other thyroid specific genes investigated in the cancer cell line. In the normal thyroid cell line, TSA increased TSH-R mRNA levels in 72 hours and created no important differences in other genes. ATRA repressed the TSH-R mRNA levels in the normal thyroid cell line and increased the TPO and Tg mRNA levels slightly in both cell lines. Furthermore, in short-term treatment, ATRA repressed NIS gene expression slightly, but in the long term, this repression turned to basal levels. 5-Aza, TSA, and ATRA did not make any differences in RAI uptake in the cancer cell line, but rTSH increased RAI uptake significantly. In the normal thyroid cell line, TSA and ATRA decreased RAI uptake (to 1/10 and 1/2, respectively), but 5-Aza and rTSH increased RAI uptake significantly (2- and 4-fold, respectively). We have shown an increase in TSH-R gene expression and radioiodine uptake with 5-Aza. Further in vitro and in vivo studies are needed to support our findings and the potential clinical use of this agent.
Open Access
Studies on estradiol dependent transcriptional regulation of human Sodium Iodide Symporter gene in mammary glands
(2002) Gülbağcı, Neriman Tuba
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.