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Updated: Jun 2, 2026
Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
Different biological effect of estrogen receptor-related receptor α in estrogen receptor-positive and -negative
Min Gao1, Peng-Ming Sun, Jian-Liu Wang
1Department of Obstetrics and Gynecology, Peking University People's Hospital, 100044 Beijing, P.R. China. gaomin202@hotmail.com.
Abstract:
Estrogen receptor-related receptor α (ERRα) has been identified as a nuclear transfactor closely related to estrogen receptor α (ERα). ERRα interferes with ER-mediated signaling pathways through competition with ERα for the common DNA sites and coregulators. Thus, it may participate in the tumorigenesis of estrogen-related cancers. To elucidate the roles of ERRα in endometrial carcinogenesis and the crosstalk between ERα and ERRα, endometrial carcinoma Ishikawa and HEC-IA cells were treated with different concentrations of 17β-E2 and/or the pure anti-estrogen drug ICI182,780. Using semi-quantitative RT-PCR and Western blot analysis, we found that 17β-E2 down-regulated the expression of ERRα in ER-positive Ishikawa cells, while up-regulating the expression of ERRα in ER-negative HEC-IA cells. Down-regulation in Ishikawa cells was furthermore found to be largely abrogated by ICI182,780. Additionally, we constructed endometrial carcinoma cell lines with overexpression of ERRα by stable transfection, renaming these Ishikawa/ERRα and HEC-IA/ERRα, respectively. To investigate the effect of ERRα overexpression on the biological behavior of the cells, MTT assay and flow cytometry analysis were performed in the constructed cell lines. In ER-positive Ishikawa cells, the overexpression of ERRα inhibited cell growth in the presence of 17β-E2, an inhibitory effect that might be due to a G0-G1 cell cycle arrest. In contrast, overexpression of ERRα stimulated cell proliferation in ER-negative HEC-IA cells independently of 17β-E2. This accelerated action was associated with changes in cell cycle distribution. Our study demonstrates that, in addition to ER, ERRα seems to be an important regulator in endometrial carcinogenesis, playing different roles in estrogen-dependent and -independent endometrial carcinomas. ERRα might modulate the ER-mediated pathways via interference with ERα transcription in endometrial carcinoma cells.
Insights
Estrogen receptor-related receptor α (ERRα) plays a dual role in endometrial cancer, inhibiting growth in estrogen-dependent cancers and promoting it in estrogen-independent ones.
Area of Science:
- Endocrinology and Cancer Biology
- Molecular Oncology
- Cell Cycle Regulation
Background:
- Estrogen receptor-related receptor α (ERRα) is structurally similar to estrogen receptor α (ERα) and can interfere with ERα-mediated signaling.
- ERRα's role in endometrial carcinogenesis and its interaction with ERα are not fully understood.
- Endometrial cancer is a significant health concern, with estrogen playing a key role in its development.
Purpose of the Study:
- To investigate the role of ERRα in endometrial carcinogenesis.
- To elucidate the crosstalk between ERα and ERRα in endometrial carcinoma cells.
- To determine how ERRα affects cell growth and proliferation in different endometrial cancer contexts.
Main Methods:
- Utilized semi-quantitative RT-PCR and Western blot analysis to assess ERRα expression.
- Treated ER-positive (Ishikawa) and ER-negative (HEC-IA) endometrial carcinoma cells with 17β-estradiol (17β-E2) and ICI182,780.
- Created stable cell lines overexpressing ERRα for functional studies using MTT assays and flow cytometry.
Main Results:
- 17β-E2 down-regulated ERRα in ER-positive cells and up-regulated it in ER-negative cells; ICI182,780 partially blocked this down-regulation.
- Overexpression of ERRα inhibited 17β-E2-induced cell growth in ER-positive cells, causing G0-G1 cell cycle arrest.
- Overexpression of ERRα promoted cell proliferation in ER-negative cells, independent of 17β-E2, with altered cell cycle distribution.
Conclusions:
- ERRα is a significant regulator in endometrial carcinogenesis, exhibiting distinct roles in estrogen-dependent and -independent cancers.
- ERRα may modulate ER-mediated pathways by interfering with ERα transcription in endometrial carcinoma.
- Targeting ERRα could offer novel therapeutic strategies for specific subtypes of endometrial cancer.
