Functional modulation of estrogen receptor by redox state with reference to thioredoxin as a mediator

Shin Ichi Hayashi, Kyoko Hajiro-Nakanishi, Yuichi Makino, Hidetaka Eguchi, Junji Yodoi, Hirotoshi Tanaka

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

Redox regulation of transcription factors has recently been demonstrated for AP-1, NF-κB, Sp-1 and glucocorticoid receptor in vitro and in vivo. The redox state in estrogen-dependent cells possibly influences the function of estrogen receptor (ER), and the regulation of the function of ER is essential for understanding of growth and differentiation of these cells, as well as promotion and progression of estrogen-associated cancer. In this paper, we first analyzed the effects of redox state on transcriptional activity of ER in terms of pS2 mRNA expression and transfection of ERE-CAT plasmid in human breast cancer cells. Addition of H2O2 at low concentrations lowered levels of pS2 mRNA and also down-regulated ERE-CAT activity, which was recovered by transfection of thioredoxin (TRX) expression vector. Next, the transfection of antisense TRX plasmid diminished ERE-CAT activity, and the activity was recovered by co-transfected sense TRX. Furthermore, specific DNA binding activity of recombinant ER was inhibited by sulfhydryl-modifying reagents and restored by the addition of recombinant TRX protein in electrophoretic mobility shift assay. These results in vitro and in vivo revealed that the transcription activity of ER is strongly influenced by its redox state, which is reversibly modulated by endogenous redox effector protein, TRX.

Original languageEnglish
Pages (from-to)4035-4040
Number of pages6
JournalNucleic acids research
Volume25
Issue number20
DOIs
Publication statusPublished - 1997 Oct 15

ASJC Scopus subject areas

  • Genetics

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