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Updated: Aug 16, 2026
Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Estrogen receptor-alpha regulates SOCS-3 expression in human breast cancer cells
Jason Matthews1, Tova Almlöf, Silke Kietz
1Department of Biosciences at Novum, Karolinska Institutet, Novum, S-14157 Huddinge, Sweden. jason.matthews@biosci.ki.se
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.
Insights
Estrogen (E2) directly increases suppressor of cytokine signalling-3 (SOCS-3) mRNA in breast cancer cells. This occurs via estrogen receptor alpha (ERalpha) binding to the SOCS-3 promoter, modulating cytokine activity.
Area of Science:
- Molecular Biology
- Endocrinology
- Cancer Research
Background:
- The suppressor of cytokine signalling (SOCS) protein family is crucial for regulating cytokine signaling pathways.
- Dysregulation of cytokine signaling is implicated in the development and progression of breast cancer.
Purpose of the Study:
- To investigate the effect of estrogen (E2) on SOCS-3 expression in human breast cancer cells.
- To elucidate the molecular mechanism by which E2 influences SOCS-3 gene expression.
Main Methods:
- Real-time PCR to quantify SOCS-3 mRNA levels.
- Reporter gene assays to assess promoter activity.
- Chromatin immunoprecipitation (ChIP) to detect ERalpha binding.
Main Results:
- E2 treatment led to a ligand- and time-dependent increase in SOCS-3 mRNA in T47D cells.
- An estrogen response element (ERE) motif was identified in the SOCS-3 promoter region.
- E2 and genistein increased reporter gene activity driven by the SOCS-3 promoter, inhibited by ICI 182,780.
- E2 induced time-dependent recruitment of ERalpha to the SOCS-3 promoter.
Conclusions:
- Estrogen receptor alpha (ERalpha) directly regulates the human SOCS-3 promoter activity in breast cancer cells.
- This direct regulation by ERalpha modulates SOCS-3 expression and consequently impacts cytokine activity in breast cancer.
