TY - JOUR
T1 - Functional modulation of estrogen receptor by redox state with reference to thioredoxin as a mediator
AU - Hayashi, Shin Ichi
AU - Hajiro-Nakanishi, Kyoko
AU - Makino, Yuichi
AU - Eguchi, Hidetaka
AU - Yodoi, Junji
AU - Tanaka, Hirotoshi
N1 - Funding Information:
We thank Drs Benita S. Katzenellenbogen (University of Illinois, Urbana, IL), Hisaji Oshima (NIH, Bethesda, MD) for providing plasmid, and Dr Masakazu Toi (The Tokyo Metropolitan Institute for Medicinal Sciences) for providing cell line. We thank Drs Kei Nakachi, and Hirota Fujiki (Saitama Cancer Center Research Institute) for valuable comments. This study was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan and for a 2nd-Term Comprehensive 10-Years Strategy for Cancer Control from the Ministry of Health and Welfare of Japan.
PY - 1997/10/15
Y1 - 1997/10/15
N2 - 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.
AB - 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.
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U2 - 10.1093/nar/25.20.4035
DO - 10.1093/nar/25.20.4035
M3 - Article
C2 - 9321654
AN - SCOPUS:0030838711
VL - 25
SP - 4035
EP - 4040
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 20
ER -
