ArticleOncotarget2015
Activation of AKR1C1/ERβ induces apoptosis by downregulation of c-FLIP in prostate cancer cells: A prospective therapeutic opportunity.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Role of Aldo-Keto reductase family 1 member C in cancer progression: a special focus on the role of AKR1C1 in pancreatic cancer.Medical oncology (Northwood, London, England) · 2025Article
- The Pros and Cons of Estrogens in Prostate Cancer: An Update with a Focus on Phytoestrogens.Biomedicines · 2024Review
- Inaugurating a novel adjuvant therapy in urological cancers: Ferroptosis.Cancer pathogenesis and therapy · 2023Review
- Article
- Article
- Review
- Estrogen Receptors-Mediated Apoptosis in Hormone-Dependent Cancers.International journal of molecular sciences · 2022Review
- Transcript Levels of Aldo-Keto Reductase Family 1 Subfamily C (AKR1C) Are Increased in Prostate Tissue of Patients with Type 2 Diabetes.Journal of personalized medicine · 2020Article
- Combined analysis of RNA-sequence and microarray data reveals effective metabolism-based prognostic signature for neuroblastoma.Journal of cellular and molecular medicine · 2020Article
- Simultaneous Targeting of Two Master Regulators of Apoptosis with Dual-Action PNA- and DNA-Peptide Conjugates.Bioconjugate chemistry · 2020Article
- Loss of AKR1C1 is a good prognostic factor in advanced NPC cases and increases chemosensitivity to cisplatin in NPC cells.Journal of cellular and molecular medicine · 2020Article
- Receptor tyrosine kinase recepteur d'origine nantais as predictive marker for aggressive prostate cancer in African Americans.Molecular carcinogenesis · 2019Article
- BRCA1 Interacting Protein COBRA1 Facilitates Adaptation to Castrate-Resistant Growth Conditions.International journal of molecular sciences · 2018Article
- Article
- The roles of AKR1C1 and AKR1C2 in ethyl-3,4-dihydroxybenzoate induced esophageal squamous cell carcinoma cell death.Oncotarget · 2016Article
- Classical and Non-Classical Roles for Pre-Receptor Control of DHT Metabolism in Prostate Cancer Progression.Hormones & cancer · 2016Review
- Oestrogens and oestrogen receptors in prostate cancer.SpringerPlus · 2016Review
- Inactivation of PI3-K/Akt and reduction of SP1 and p65 expression increase the effect of solamargine on suppressing EP4 expression in human lung cancer cells.Journal of experimental & clinical cancer research : CR · 2015Article
- Changes in Estrogen Receptor ERβ (ESR2) Expression without Changes in the Estradiol Levels in the Prostate of Aging Rats.PloS one · 2015Article
- The resurgence of estrogens in the treatment of castration-resistant prostate cancer.Indian journal of urology : IJU : journal of the Urological Society of IndiaReview
Corrections and comments
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Authors and funding
5 authors at 5 institutions in 2 countries.
Funding
Abstract
We provide first-time evidence for ERβ-mediated transcriptional upregulation of c-FLIP as an underlying mechanism in the development of castrate-resistant cancer. While androgens inhibit apoptosis partly through transcriptional upregulation of the anti-apoptotic protein, c-FLIP in androgen-responsive cells, they downregulate c-FLIP in androgen-independent cells. We found that although Sp1 and p65 trans-activate c-FLIP, the combination of Sp1 and p65 has differential effects in a cellular context-dependent manner. We show that activation of the androgen metabolism enzyme, aldo-keto reductase, AKR1C1, relieves androgen independence through activation of 3β-Adiol-mediated upregulation of ERβ. ERβ competes with Sp1 and Sp3 to transcriptionally downregulate c-FLIP in the absence of consensus estrogen-response element in androgen-independent cells. Forced expression of AR in androgen-independent cells show that ERβ-mediated growth inhibition occurs under conditions of androgen independence. Reactivation of ERβ with the estrogenic metabolite, 2-methoxyestradiol, decreased enrichment ratio of Sp1/Sp3 at the c-FLIP promoter with concomitant effects on cell growth and death. Expression of Sp1 and c-FLIP are elevated while AKR1C1, ERβ and Sp3 are significantly low in human prostate tumor samples. ERβ is epigenetically silenced in prostate cancer patients, therefore our results suggest that combination of ERβ agonists with ADT would benefit men stratified on the basis of high estrogen levels.
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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.