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

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      Author(s)
      Alotaibi, H.
      Yaman, E. C.
      Demirpence, E.
      Tazebay, U. H.
      Date
      2006
      Source Title
      Biochemical and Biophysical Research Communications
      Print ISSN
      0006-291X
      Publisher
      Elsevier
      Volume
      345
      Issue
      4
      Pages
      1487 - 1496
      Language
      English
      Type
      Article
      Item Usage Stats
      114
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      102
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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.
      Keywords
      Iodide Transport
      Nis
      Estrogen Receptor
      Mammary Gland
      Breast Cancer
      Permalink
      http://hdl.handle.net/11693/11504
      Published Version (Please cite this version)
      http://dx.doi.org/10.1016/j.bbrc.2006.05.049
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