Unliganded estrogen receptor-alpha activates transcription of the mammary gland Na+/I- symporter gene.
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.
Alotaibi
Hani
H
Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey.
Yaman
Elif Cankaya
EC
Demirpençe
Ediz
E
Tazebay
Uygar H
UH
D001483:Base Sequence; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D034622:RNA Interference; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D000072482:Retinoic Acid Receptor alpha; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*; D014212:Tretinoin / Q000494:pharmacology; D000099209:Sodium-Iodide Symporters
D047628:Estrogen Receptor alpha; D008024:Ligands; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D027981:Symporters; D014212:Tretinoin; D000099209:Sodium-Iodide Symporters; C000607071:RARA protein, human