Estrogen receptor-α regulates SOCS-3 expression in human breast cancer cells

Jason Matthews; Tova Almlöf; Silke Kietz; Jörg Leers; Jan Åke Gustafsson

doi:10.1016/j.bbrc.2005.07.057

Estrogen receptor-α regulates SOCS-3 expression in human breast cancer cells

Jason Matthews, Tova Almlöf, Silke Kietz, Jörg Leers, Jan Åke Gustafsson

Research output: Contribution to journal › Article › peer-review

34 Scopus citations

Abstract

The suppressor of cytokine signalling (SOCS) protein family negatively regulates cytokine action. In this study, we investigated the effects of estrogen (E2) on SOCS-3 expression in T47D and MCF-7 human breast cancer cells. Real-time PCR analysis of E2-treated T47D cells revealed a ligand and time-dependent increase in of SOCS-3 mRNA levels. Cloning of a 1.7 kb fragment of the human SOCS-3 5′ flanking sequence, and subsequent analysis of potential transcription factor-binding sites identified an incomplete ERE motif located -1493 to -1489 upstream of the start site. Transient transfection of the cloned fragment in MCF-7 cells showed that both E2 and genistein treatment caused an increase in reporter gene activity, which was inhibited by co-treatment with ICI 182,780. Chromatin immunoprecipitation analysis revealed an E2 and time-dependent recruitment of ERα to the E2 responsive region of the human SOCS-3 promoter. In summary, this study shows that ERα directly regulates human SOCS-3 promoter activity in human breast cancer cells, thus modulating cytokine activity.

Original language	English (US)
Pages (from-to)	168-174
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	335
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2005.07.057
State	Published - Sep 16 2005

Keywords

Chromatin immunoprecipitation
Cytokine
Estrogen receptor
Nuclear receptor
Promoter cloning
SOCS-3
STAT

ASJC Scopus subject areas

Biochemistry
Biophysics
Molecular Biology

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title = "Estrogen receptor-α regulates SOCS-3 expression in human breast cancer cells",

abstract = "The suppressor of cytokine signalling (SOCS) protein family negatively regulates cytokine action. In this study, we investigated the effects of estrogen (E2) on SOCS-3 expression in T47D and MCF-7 human breast cancer cells. Real-time PCR analysis of E2-treated T47D cells revealed a ligand and time-dependent increase in of SOCS-3 mRNA levels. Cloning of a 1.7 kb fragment of the human SOCS-3 5′ flanking sequence, and subsequent analysis of potential transcription factor-binding sites identified an incomplete ERE motif located -1493 to -1489 upstream of the start site. Transient transfection of the cloned fragment in MCF-7 cells showed that both E2 and genistein treatment caused an increase in reporter gene activity, which was inhibited by co-treatment with ICI 182,780. Chromatin immunoprecipitation analysis revealed an E2 and time-dependent recruitment of ERα to the E2 responsive region of the human SOCS-3 promoter. In summary, this study shows that ERα directly regulates human SOCS-3 promoter activity in human breast cancer cells, thus modulating cytokine activity.",

keywords = "Chromatin immunoprecipitation, Cytokine, Estrogen receptor, Nuclear receptor, Promoter cloning, SOCS-3, STAT",

author = "Jason Matthews and Tova Alml{\"o}f and Silke Kietz and J{\"o}rg Leers and Gustafsson, {Jan {\AA}ke}",

note = "Funding Information: The authors thank all members of the Receptor Biology Unit for their assistance and helpful discussions during this study. This study was supported by a postdoctoral fellowship from the David and Astrid Hagel{\'e}ns Foundation (to J.M.) and by grants from the Swedish Cancer Fund and KaroBio AB.",

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AU - Matthews, Jason

AU - Almlöf, Tova

AU - Kietz, Silke

AU - Leers, Jörg

AU - Gustafsson, Jan Åke

N1 - Funding Information: The authors thank all members of the Receptor Biology Unit for their assistance and helpful discussions during this study. This study was supported by a postdoctoral fellowship from the David and Astrid Hageléns Foundation (to J.M.) and by grants from the Swedish Cancer Fund and KaroBio AB.

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Y1 - 2005/9/16

N2 - The suppressor of cytokine signalling (SOCS) protein family negatively regulates cytokine action. In this study, we investigated the effects of estrogen (E2) on SOCS-3 expression in T47D and MCF-7 human breast cancer cells. Real-time PCR analysis of E2-treated T47D cells revealed a ligand and time-dependent increase in of SOCS-3 mRNA levels. Cloning of a 1.7 kb fragment of the human SOCS-3 5′ flanking sequence, and subsequent analysis of potential transcription factor-binding sites identified an incomplete ERE motif located -1493 to -1489 upstream of the start site. Transient transfection of the cloned fragment in MCF-7 cells showed that both E2 and genistein treatment caused an increase in reporter gene activity, which was inhibited by co-treatment with ICI 182,780. Chromatin immunoprecipitation analysis revealed an E2 and time-dependent recruitment of ERα to the E2 responsive region of the human SOCS-3 promoter. In summary, this study shows that ERα directly regulates human SOCS-3 promoter activity in human breast cancer cells, thus modulating cytokine activity.

AB - The suppressor of cytokine signalling (SOCS) protein family negatively regulates cytokine action. In this study, we investigated the effects of estrogen (E2) on SOCS-3 expression in T47D and MCF-7 human breast cancer cells. Real-time PCR analysis of E2-treated T47D cells revealed a ligand and time-dependent increase in of SOCS-3 mRNA levels. Cloning of a 1.7 kb fragment of the human SOCS-3 5′ flanking sequence, and subsequent analysis of potential transcription factor-binding sites identified an incomplete ERE motif located -1493 to -1489 upstream of the start site. Transient transfection of the cloned fragment in MCF-7 cells showed that both E2 and genistein treatment caused an increase in reporter gene activity, which was inhibited by co-treatment with ICI 182,780. Chromatin immunoprecipitation analysis revealed an E2 and time-dependent recruitment of ERα to the E2 responsive region of the human SOCS-3 promoter. In summary, this study shows that ERα directly regulates human SOCS-3 promoter activity in human breast cancer cells, thus modulating cytokine activity.

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Estrogen receptor-α regulates SOCS-3 expression in human breast cancer cells

Abstract

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