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Updated: Aug 14, 2026
Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Estrogen receptor-alpha mediates gene expression changes and growth response in ovarian cancer cells exposed to
Amanda J M O'Donnell1, Kenneth G Macleod, David J Burns
1Cancer Research UK Centre, University of Edinburgh.
Abstract:
Estrogens play a significant role in the development, growth, invasion and metastasis of ovarian tumors. The transcriptional program regulated by 17beta-estradiol (E(2)) in human ovarian cancer cell lines was analyzed using cDNA microarrays containing 1200 cancer-related genes. Twenty-eight transcripts had at least a threefold change in expression in E(2)-treated PEO1 ovarian carcinoma cells compared with controls. These differences were confirmed by real-time quantitative PCR and shown to be dependent upon the expression of functional estrogen receptor-alpha (ERalpha). Consistent with this, these gene expression changes were blocked by the anti-estrogen tamoxifen. The use of ERalpha- and ERbeta-specific ligands allowed molecular dissection of the E(2) response and showed that ERalpha activation was responsible for the observed changes in gene expression, whereas ERbeta played no significant role. Inhibition of de novo protein synthesis by cycloheximide was used to distinguish between primary and secondary target genes regulated by E(2). Actinomycin D was used to show that changes in gene expression levels induced by E(2) were a result of changes in transcription and not due to changes in mRNA stability. The results presented here demonstrate that estrogen-driven growth of epithelial ovarian carcinoma is mediated by activation of ERalpha-mediated, and not ERbeta-mediated, transcription.
Insights
Estrogen drives ovarian cancer growth primarily through estrogen receptor-alpha (ERalpha) activation. This study reveals ERalpha-mediated transcription, not ERbeta, is key for estrogen
Area of Science:
- Oncology
- Molecular Biology
- Endocrinology
Background:
- Estrogens are implicated in ovarian tumor development, invasion, and metastasis.
- Understanding estrogen's molecular mechanisms in ovarian cancer is crucial for targeted therapies.
Purpose of the Study:
- To analyze the transcriptional program regulated by 17beta-estradiol (E(2)) in human ovarian cancer cells.
- To determine the specific role of estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta) in mediating these transcriptional changes.
Main Methods:
- cDNA microarrays were used to analyze gene expression in E(2)-treated ovarian cancer cells.
- Real-time quantitative PCR confirmed transcript changes.
- ERalpha- and ERbeta-specific ligands, tamoxifen, cycloheximide, and actinomycin D were employed to dissect molecular pathways.
Main Results:
- Twenty-eight transcripts showed at least a threefold change in expression following E(2) treatment.
- Gene expression changes were dependent on functional ERalpha and blocked by tamoxifen.
- ERalpha activation mediated the observed transcriptional changes, while ERbeta played no significant role.
- E(2)-induced gene expression changes resulted from altered transcription, not mRNA stability.
Conclusions:
- Estrogen-driven growth of epithelial ovarian carcinoma is mediated by ERalpha-mediated transcription.
- ERbeta does not play a significant role in mediating estrogen's effects on ovarian cancer gene expression.
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