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 journalArticlepeer-review

33 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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