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 journalArticle

31 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 languageEnglish (US)
Pages (from-to)168-174
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume335
Issue number1
DOIs
StatePublished - 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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