ArticleThe Prostate2016
NF-κB and androgen receptor variant 7 induce expression of SRD5A isoforms and confer 5ARI resistance.
Article in The Prostate, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04288427 (5-Alpha Reductase 2 as a Marker of Resistance to 5ARI Therapy), which is not on this map. Cited by 16 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
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.
5-Alpha Reductase 2 as a Marker of Resistance to 5ARI Therapy
Who cites it
16 citing papers in PubMed, 40 citations in OpenAlex.
- SRD5A2 and emerging therapies in androgen-driven disorders.Nature reviews. Urology · 2026Review
- Decoding benign prostatic hyperplasia at single-cell resolution: heterogeneity, inflammation, and beyond androgen-driven pathogenesis.Frontiers in immunology · 2026Review
- Intratumoral Androgens and Genetic Variants Driving Therapy Resistance in Prostate Cancer.Research (Washington, D.C.) · 2026Review
- Microbiome analysis reveals the inducing effect ofVirulence · 2024Article
- Intrinsic and extrinsic factors causing hyperplasia of the prostate.International journal of urology : official journal of the Japanese Urological Association · 2024Review
- Polygenic risk score predicting susceptibility and outcome of benign prostatic hyperplasia in the Han Chinese.Human genomics · 2024Article
- Exploring the Enigma of 5-ARIs Resistance in Benign Prostatic Hyperplasia: Paving the Path for Personalized Medicine.Current urology reports · 2023Review
- Two genetic variants in the SRD5A2 gene are found to be associated with sex differences in the disease characteristics of patients with chronic hepatitis B virus infection.Biology of sex differences · 2023Article
- Upregulation of mir-1199-5p is associated with reduced type 2 5-α reductase expression in benign prostatic hyperplasia.BMC urology · 2022Article
- Glucocorticoids are induced while dihydrotestosterone levels are suppressed in 5-alpha reductase inhibitor treated human benign prostate hyperplasia patients.The Prostate · 2022Article
- TNF is a potential therapeutic target to suppress prostatic inflammation and hyperplasia in autoimmune disease.Nature communications · 2022Article
- The role of the androgen receptor in prostate development and benign prostatic hyperplasia: A review.Asian journal of urology · 2020Review
- Hyperglycemia and T Cell infiltration are associated with stromal and epithelial prostatic hyperplasia in the nonobese diabetic mouse.The Prostate · 2019Article
- Enabling precision medicine by unravelling disease pathophysiology: quantifying signal transduction pathway activity across cell and tissue types.Scientific reports · 2019Article
- Inflammation and NF-κB Signaling in Prostate Cancer: Mechanisms and Clinical Implications.Cells · 2018Review
- Activation of GRP/GRP-R signaling contributes to castration-resistant prostate cancer progression.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundBenign prostatic hyperplasia (BPH) is treated with 5α-reductase inhibitors (5ARI). These drugs inhibit the conversion of testosterone to dihydrotestosterone resulting in apoptosis and prostate shrinkage. Most patients initially respond to 5ARIs; however, failure is common especially in inflamed prostates, and often results in surgery. This communication examines a link between activation of NF-κB and increased expression of SRD5A2 as a potential mechanism by which patients fail 5ARI therapy.
methodsTissue was collected from "Surgical" patients, treated specifically for lower urinary tract symptoms secondary to advanced BPH; and, cancer free transition zone from "Incidental" patients treated for low grade, localized peripheral zone prostate cancer. Clinical, molecular and histopathological profiles were analyzed. Human prostatic stromal and epithelial cell lines were genetically modified to regulate NF-κB activity, androgen receptor (AR) full length (AR-FL), and AR variant 7 (AR-V7) expression.
resultsSRD5A2 is upregulated in advanced BPH. SRD5A2 was significantly associated with prostate volume determined by Transrectal Ultrasound (TRUS), and with more severe lower urinary tract symptoms (LUTS) determined by American Urological Association Symptom Score (AUASS). Synthesis of androgens was seen in cells in which NF-κB was activated. AR-FL and AR-V7 expression increased SRD5A2 expression while forced activation of NF-κB increased all three SRD5A isoforms. Knockdown of SRD5A2 in the epithelial cells resulted in significant reduction in proliferation, AR target gene expression, and response to testosterone (T). In tissue recombinants, canonical NF-κB activation in prostatic epithelium elevated all three SRD5A isoforms and resulted in in vivo growth under castrated conditions.
conclusionIncreased BPH severity in patients correlates with SRD5A2 expression. We demonstrate that NF-κB and AR-V7 upregulate SRD5A expression providing a mechanism to explain failure of 5ARI therapy in BPH patients. Prostate 76:1004-1018, 2016. © 2016 Wiley Periodicals, Inc.
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