Related Experiment Video
Updated: Jun 8, 2026

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Estrogen-related receptor γ modulates cell proliferation and estrogen signaling in breast cancer
Nobuhiro Ijichi1, Takashi Shigekawa, Kazuhiro Ikeda
1Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
Abstract:
Breast cancer is primarily a hormone-dependent tumor that can be regulated by status of steroid hormones including estrogen and progesterone. Estrogen-related receptors (ERRs) are orphan nuclear receptors most closely related to estrogen receptor (ER) and much attention has been recently paid to the functions of ERRs in breast cancer in terms of the interactions with ER. In the present study, we investigated the expression of ERRγ in human invasive breast cancers by immunohistochemical analysis (n=110) obtained by radical mastectomy. Nuclear immunoreactivity of ERRγ was detected in 87 cases (79%) and tended to correlate with the lymph node status. No significant associations were observed with other clinicopathological characteristics, including the expression levels of both estrogen and progesterone receptors. In MCF-7 breast cancer cells, we demonstrated that ERRγ mRNA was up-regulated dose-dependently by estrogen, and that this up-regulation of ERRγ mRNA by estrogen was abolished by ICI 182,780 treatment. We also demonstrated that exogenously transfected ERRγ increased MCF-7 cell proliferation. Furthermore, ERRγ enhanced estrogen response element (ERE)-driven transcription in MCF-7 cells. In 293T cells, ERRγ could also stimulate ERE-mediated transcription with or without ERα. These results suggest that ERRγ plays an important role as a modulator of estrogen signaling in breast cancer cells.
Insights
Estrogen-related receptor gamma (ERRγ) is frequently expressed in breast cancer and promotes cell proliferation. Estrogen up-regulates ERRγ, suggesting ERRγ modulates estrogen signaling in hormone-dependent breast cancer.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Breast cancer is often hormone-dependent, influenced by estrogen and progesterone.
- Estrogen-related receptors (ERRs) are structurally similar to estrogen receptors (ERs) and are implicated in breast cancer progression.
- The specific role of ERRγ in breast cancer and its interaction with estrogen signaling requires further elucidation.
Purpose of the Study:
- To investigate the expression of ERRγ in human invasive breast cancers.
- To determine the relationship between ERRγ expression and clinicopathological characteristics.
- To explore the functional role of ERRγ in estrogen signaling and breast cancer cell proliferation.
Main Methods:
- Immunohistochemical analysis of ERRγ expression in 110 human invasive breast cancer samples.
- In vitro studies using MCF-7 and 293T cells to assess ERRγ mRNA regulation by estrogen and its effect on cell proliferation and transcriptional activity.
- Treatment with estrogen and ICI 182,780 to evaluate estrogen-dependent regulation of ERRγ.
Main Results:
- Nuclear ERRγ immunoreactivity was detected in 79% of breast cancer cases and correlated with lymph node status.
- Estrogen dose-dependently up-regulated ERRγ mRNA in MCF-7 cells, an effect blocked by ICI 182,780.
- Overexpression of ERRγ increased MCF-7 cell proliferation and enhanced estrogen response element (ERE)-driven transcription, with or without ERα.
Conclusions:
- ERRγ is frequently expressed in invasive breast cancer and may serve as a prognostic marker.
- Estrogen signaling positively regulates ERRγ expression in breast cancer cells.
- ERRγ functions as a modulator of estrogen signaling, promoting breast cancer cell proliferation and transcriptional activity.
Related Concept Videos
Mitogens and the Cell Cycle
Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
TGF - β Signaling Pathway
Transducer Mechanism: Nuclear Receptors
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
