Unliganded estrogen receptor-x activates transcription of the mammary gland Na+/I-symporter gene

Date
2006
Authors
Alotaibi, H.
Yaman, E. C.
Demirpence, E.
Tazebay, U. H.
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Source Title
Biochemical and Biophysical Research Communications
Print ISSN
0006-291X
Electronic ISSN
Publisher
Elsevier
Volume
345
Issue
4
Pages
1487 - 1496
Language
English
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Abstract

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- a (ERa) positive cells and we investigated the role of ERa in the regulation of NIS expression. We showed that the suppression of endogenous ERa by RNA interference downregulates NIS expression in ERa positive mammary cells. Besides, in an ERa negative cell line, reintroduction of ERa 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 ERa and mediates ERa-dependent activation of transcription. Our results indicate that unliganded ERa (apo-ERa) contributes to the regulation of NIS gene expression. 2006 Elsevier Inc. All rights reserved.

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