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Thioredoxin and thioredoxin reductase influence estrogen receptor alpha-mediated gene expression in human breast cancer cells

Academic Article
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Overview

authors

  • Rao, A. K.
  • Ziegler, Y. S.
  • McLeod, I. X.
  • Yates III, John
  • Nardulli, A. M.

publication date

  • 2009

journal

  • Journal of Molecular Endocrinology  Journal

abstract

  • Accumulation of reactive oxygen species (ROS) in cells damages resident proteins, lipids, and DNA. In order to overcome the oxidative stress that occurs with ROS accumulation, cells must balance free radical production with an increase in the level of antioxidant enzymes that convert free radicals to less harmful species. We identified two antioxidant enzymes, thioredoxin (Trx) and Trx reductase (TrxR), in a complex associated with the DNA-bound estrogen receptor alpha (ERalpha). Western analysis and immunocytochemistry were used to demonstrate that Trx and TrxR are expressed in the cytoplasm and in the nuclei of MCF-7 human breast cancer cells. More importantly, endogenously expressed ERalpha, Trx, and TrxR interact and ERalpha and TrxR associate with the native, estrogen-responsive pS2 and progesterone receptor genes in MCF-7 cells. RNA interference assays demonstrated that Trx and TrxR differentially influence estrogen-responsive gene expression and that together, 17beta-estradiol, Trx, and TrxR alter hydrogen peroxide (H(2)O(2)) levels in MCF-7 cells. Our findings suggest that Trx and TrxR are multifunctional proteins that, in addition to modulating H(2)O(2) levels and transcription factor activity, aid ERalpha in regulating the expression of estrogen-responsive genes in target cells.

subject areas

  • Blotting, Western
  • Cell Line, Tumor
  • Chromatin Immunoprecipitation
  • Estrogen Receptor alpha
  • Ethanol
  • Gene Expression
  • Humans
  • Hydrogen Peroxide
  • Immunohistochemistry
  • Immunoprecipitation
  • Oxidative Stress
  • Protein Binding
  • RNA Interference
  • Thioredoxin-Disulfide Reductase
  • Thioredoxins
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Identity

PubMed Central ID

  • PMC2994277

International Standard Serial Number (ISSN)

  • 0952-5041

Digital Object Identifier (DOI)

  • 10.1677/jme-09-0053

PubMed ID

  • 19620238
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Additional Document Info

start page

  • 251

end page

  • 261

volume

  • 43

issue

  • 5-6

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