Estrogen receptor-alpha 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 ERalpha to the E2 responsive region of the human SOCS-3 promoter. In summary, this study shows that ERalpha directly regulates human SOCS-3 promoter activity in human breast cancer cells, thus modulating cytokine activity.

• Authors: Jason Matthews, Tova Almlöf, Silke Kietz, Jörg Leers, Jan-Ake Gustafsson
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 335 Issue 1 Pg. 168-74 (Sep 16 2005) ISSN: 0006-291X [Print] United States
• PMID: 16055089 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Estrogen Receptor alpha
• Repressor Proteins
• SOCS3 protein, human
• Suppressor of Cytokine Signaling 3 Protein
• Suppressor of Cytokine Signaling Proteins
• Transcription Factors

Topics

• Base Sequence
• Breast Neoplasms (genetics, metabolism)
• Cell Line, Tumor
• Cloning, Molecular
• Estrogen Receptor alpha (metabolism)
• Gene Expression Regulation, Neoplastic
• Humans
• Molecular Sequence Data
• Promoter Regions, Genetic (genetics)
• Repressor Proteins (genetics, metabolism)
• Suppressor of Cytokine Signaling 3 Protein
• Suppressor of Cytokine Signaling Proteins
• Transcription Factors (genetics, metabolism)