ArticleBreast cancer research and treatment2009
The androgen metabolite 5alpha-androstane-3beta,17beta-diol (3betaAdiol) induces breast cancer growth via estrogen receptor: implications for aromatase inhibitor resistance.
Article in Breast cancer research and treatment, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 76 citations in OpenAlex.
- Sex-Biased Immunity: The Hidden Variable in Immuno-oncology.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
- Intracrine Formation of Steroid Hormones in Breast Cancer, Epidermal Keratinocyte, Dermal Fibroblast, and Adipocyte Cell Lines Measured by LC-MS/MS.International journal of molecular sciences · 2025Article
- Loss of AR-regulated AFF3 contributes to prostate cancer progression and reduces ferroptosis sensitivity by downregulating ACSL4 based on single-cell sequencing analysis.Apoptosis : an international journal on programmed cell death · 2024Article
- Association of HSD3B1 Genotype and Clinical Outcomes in Postmenopausal Estrogen-Receptor-Positive Breast Cancer.Annals of surgical oncology · 2022Article
- Pre-Menopausal Women With Breast Cancers Having High AR/ER Ratios in the Context of Higher Circulating Testosterone Tend to Have Poorer Outcomes.Frontiers in endocrinology · 2021Article
- Review
- Metabolites of n-Butylparaben and iso-Butylparaben Exhibit Estrogenic Properties in MCF-7 and T47D Human Breast Cancer Cell Lines.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- High N-Acetyltransferase 1 Expression Is Associated with Estrogen Receptor Expression in Breast Tumors, but Is not Under Direct Regulation by Estradiol, 5The Journal of pharmacology and experimental therapeutics · 2018Article
- Post-menopausal breast cancer: from estrogen to androgen receptor.Oncotarget · 2017Review
- IRIS study: a phase II study of the steroid sulfatase inhibitor Irosustat when added to an aromatase inhibitor in ER-positive breast cancer patients.Breast cancer research and treatment · 2017Article
- Review
- Family Matters: Collaboration and Conflict Among the Steroid Receptors Raises a Need for Group Therapy.Endocrinology · 2016Review
- Cooperative Dynamics of AR and ER Activity in Breast Cancer.Molecular cancer research : MCR · 2016Article
- Endocrine Response Phenotypes Are Altered by Charcoal-Stripped Serum Variability.Endocrinology · 2016Article
- Structural and functional characterization of aromatase, estrogen receptor, and their genes in endocrine-responsive and -resistant breast cancer cells.The Journal of steroid biochemistry and molecular biology · 2016Review
- Human 3β-hydroxysteroid dehydrogenase type 1 in human breast cancer: clinical significance and prognostic associations.Cancer medicine · 2016Article
- The Metabolism, Analysis, and Targeting of Steroid Hormones in Breast and Prostate Cancer.Hormones & cancer · 2016Review
- Synergistic control of sex hormones by 17β-HSD type 7: a novel target for estrogen-dependent breast cancer.Journal of molecular cell biology · 2015Article
- Dehydroepiandrosterone-induces miR-21 transcription in HepG2 cells through estrogen receptor β and androgen receptor.Molecular and cellular endocrinology · 2014Article
- DHEA metabolites activate estrogen receptors alpha and beta.Steroids · 2013Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The aromatase inhibitors (AIs) are used to treat estrogen receptor-positive (ER+) breast tumors in post-menopausal women, and function by blocking the conversion of adrenal androgens to estrogens by the enzyme CYP19 aromatase. Breast cancer patients receiving AI therapy have circulating estrogen levels below the level of detection; however, androgen concentrations remain unchanged. We were interested in studying the effects of androgens on breast cancer cell proliferation under profound estrogen-deprived conditions. Using in vitro models of estrogen-dependent breast cancer cell growth we show that the androgens testosterone and 5alpha-dihydrotestosterone induce the growth of MCF-7, T47D and BT-474 cells in the absence of estrogen. Furthermore, we demonstrate that under profound estrogen-deprived conditions these breast cancer cells up-regulate steroidogenic enzymes that can metabolize androgens to estrogens. Lastly, we found that the downstream metabolite of 5alpha-dihydrotestosterone, 5alpha-androstane-3beta,17beta-diol (3betaAdiol), is estrogenic in breast cancer cells, and induces growth and ER-signaling via activation of ERalpha. In conclusion, our results show that breast cancer cells deprived of estrogen up-regulate steroidogenic enzymes and metabolize androgens to estrogen-like steroids. The generation of estrogen-like steroids represents a potential mechanism of resistance to aromatase inhibitors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.