Alotaibi Hani, Yaman Elif Cankaya, Demirpençe Ediz, Tazebay Uygar H
Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey.
Biochem Biophys Res Commun. 2006 Jul 14;345(4):1487-96. doi: 10.1016/j.bbrc.2006.05.049. Epub 2006 May 15.
The function of sodium iodide symporter (Na(+)/I(-) symporter, or NIS) in mammary epithelial cells is essential for the accumulation of I(-) in milk; the newborn's first source of I(-) for thyroid hormone synthesis. Furthermore, increased mammary gland NIS expression has previously been shown in human breast cancer. Several hormones and factors including all-trans-retinoic acid (tRA) regulate the expression of NIS. In this study, using breast cancer cell lines, we established that tRA-responsive NIS expression is confined to estrogen receptor-alpha (ERalpha) positive cells and we investigated the role of ERalpha in the regulation of NIS expression. We showed that the suppression of endogenous ERalpha by RNA interference downregulates NIS expression in ERalpha positive mammary cells. Besides, in an ERalpha negative cell line, reintroduction of ERalpha resulted in the expression of NIS in a ligand-independent manner. We also identified a novel estrogen-responsive element in the promoter region of NIS that specifically binds ERalpha and mediates ERalpha-dependent activation of transcription. Our results indicate that unliganded ERalpha (apo-ERalpha) contributes to the regulation of NIS gene expression.
碘化钠同向转运体（Na⁺/I⁻同向转运体，即NIS）在乳腺上皮细胞中的功能对于碘在乳汁中的蓄积至关重要；碘是新生儿甲状腺激素合成的首个碘来源。此外，先前已证实在人类乳腺癌中乳腺组织NIS表达增加。包括全反式维甲酸（tRA）在内的多种激素和因子可调节NIS的表达。在本研究中，我们利用乳腺癌细胞系证实，tRA应答性NIS表达局限于雌激素受体α（ERα）阳性细胞，并研究了ERα在NIS表达调控中的作用。我们发现，通过RNA干扰抑制内源性ERα可下调ERα阳性乳腺细胞中NIS的表达。此外，在ERα阴性细胞系中重新导入ERα会导致NIS以非配体依赖方式表达。我们还在NIS启动子区域鉴定出一个新的雌激素应答元件，该元件可特异性结合ERα并介导ERα依赖的转录激活。我们的结果表明，未结合配体的ERα（无活性ERα）参与NIS基因表达的调控。
