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Updated: Jan 5, 2026
Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Steroid enzyme and receptor expression and regulations in breast tumor samples - A statistical evaluation of public
Tang Li1, Wenfa Zhang1, Sheng-Xiang Lin1
1Axe Molecular Endocrinology and Nephrology, CHU Research Center and Department of Molecular Medicine, Laval University, 2705 Boulevard Laurier, Québec City, Québec G1V 4G2, Canada.
Abstract:
In spite of the significant progress of estrogen-dependent breast cancer (BC) treatment, aromatase inhibitor resistance is a major problem limiting the clinical benefit of this frontier endocrine-therapy. The aim of this study was to determine the differential expression of steroid-converting enzymes between tumor and adjacent normal tissues, as well as their correlation in modulating intratumoral steroid-hormone levels in post-menopausal estrogen-dependent BC. RNA sequencing dataset (n = 1097) of The-Cancer-Genome-Atlas (Breast Invasive Carcinoma) retrieved through the data portal of Genomic Data Commons was used for differential expressions and expression correlation analyses by Mann-Whitney U and Spearman's rank test, respectively. The results showed significant up-regulation of 17β-HSD7 (2.50-fold, p < 0.0001) in BC, supporting its effect in sex-hormone control. Besides, suppression of 11β-HSD1 expression (-8.29-fold, p < 0.0001) and elevation of 11β-HSD2 expression (2.04-fold, p < 0.0001) provide a low glucocorticoid environment diminishing BC anti-proliferation. Furthermore, 3α-HSDs were down-regulated (-1.59-fold, p < 0.01; -8.18-fold, p < 0.0001; -33.96-fold, p < 0.0001; -31.85-fold, p < 0.0001 for type 1-4, respectively), while 5α-reductases were up-regulated (1.41-fold, p < 0.0001; 2.85-fold, p < 0.0001; 1.70-fold, p < 0.0001 for type 1-3, respectively) in BC, reducing cell proliferation suppressers 4-pregnenes, increasing cell proliferation stimulators 5α-pregnanes. Expression analysis indicates significant correlations between 11β-HSD1 with 3α-HSD4 (r = 0.605, p < 0.0001) and 3α-HSD3 (r = 0.537, p < 0.0001). Significant expression correlations between 3α-HSDs were also observed. Our results systematically present the regulation of steroid-converting enzymes and their roles in modulating the intratumoral steroid-hormone levels in BC with a vivid 3D-schema, supporting novel therapy targeting the reductive 17β-HSD7 and proposing a new combined therapy targeting 11β-HSD2 and 17β-HSD7.
Insights
Aromatase inhibitor resistance in estrogen-dependent breast cancer (BC) is a challenge. This study reveals differential expression of steroid-converting enzymes in BC, offering novel therapeutic targets like 17β-HSD7 and combined 11β-HSD2/17β-HSD7 therapies.
Area of Science:
- Endocrinology
- Oncology
- Genomics
Background:
- Aromatase inhibitors are crucial for estrogen-dependent breast cancer (BC) treatment.
- Resistance to aromatase inhibitors remains a significant clinical challenge.
- Understanding intratumoral steroid hormone modulation is key to overcoming resistance.
Purpose of the Study:
- To investigate differential expression of steroid-converting enzymes in BC tissues versus normal adjacent tissues.
- To analyze the correlation of these enzymes in modulating intratumoral steroid hormone levels.
- To identify potential therapeutic targets for overcoming aromatase inhibitor resistance.
Main Methods:
- Utilized RNA sequencing data from The Cancer Genome Atlas (TCGA) Breast Invasive Carcinoma dataset (n=1097).
- Performed differential expression analysis using Mann-Whitney U test.
- Conducted expression correlation analysis using Spearman's rank test.
Main Results:
- Significant upregulation of 17β-HSD7 (2.50-fold) and 5α-reductases (types 1-3) observed in BC.
- Suppression of 11β-HSD1 (-8.29-fold) and upregulation of 11β-HSD2 (2.04-fold) noted, creating a low glucocorticoid environment.
- Downregulation of 3α-HSDs (types 1-4) and significant correlations between 11β-HSD1 and 3α-HSD3/4 were identified.
Conclusions:
- Steroid-converting enzyme dysregulation significantly impacts intratumoral steroid hormone levels in BC.
- Upregulated 17β-HSD7 and altered 11β-HSD1/2 expression suggest roles in BC progression and resistance.
- Targeting 17β-HSD7, or a combination of 11β-HSD2 and 17β-HSD7, presents promising novel therapeutic strategies for BC.
