ArticlePloS one2014
Nrf1 and Nrf2 transcription factors regulate androgen receptor transactivation in prostate cancer cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 68 citations in OpenAlex.
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- 5-Hydroxyeicosatetraenoic Acid Controls Androgen Reduction in Diverse Types of Human Epithelial Cells.Endocrinology · 2022Article
- The ERα-NRF2 signalling axis promotes bicalutamide resistance in prostate cancer.Cell communication and signaling : CCS · 2022Article
- The Prostate Cancer Androgen Receptor Cistrome in African American Men Associates with Upregulation of Lipid Metabolism and Immune Response.Cancer research · 2022Article
- NRF2: A crucial regulator for mitochondrial metabolic shift and prostate cancer progression.Frontiers in physiology · 2022Review
- The Role of NRF2 in Bone Metabolism - Friend or Foe?Frontiers in endocrinology · 2022Review
- Combination of the NRF2 Inhibitor and Autophagy Inhibitor Significantly Inhibited Tumorigenicity of Castration-Resistant Prostate Cancer.Computational and mathematical methods in medicine · 2022Article
- Role of NRF2 and Sirtuin activators in COVID-19.Clinical immunology (Orlando, Fla.) · 2021Review
- Oxidative stress and redox signaling in CRPC progression: therapeutic potential of clinically-tested Nrf2-activators.Cancer drug resistance (Alhambra, Calif.) · 2021Review
- Targeting immunometabolism to treat COVID-19.Immunotherapy advances · 2021Review
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- The Nrf2 Activator (DMF) and Covid-19: Is there a Possible Role?Medical archives (Sarajevo, Bosnia and Herzegovina) · 2020Review
- Overall survival prediction of non-small cell lung cancer by integrating microarray and clinical data with deep learning.Scientific reports · 2020Article
- Bardoxolone-Methyl (CDDO-Me) Suppresses Androgen Receptor and Its Splice-Variant AR-V7 and Enhances Efficacy of Enzalutamide in Prostate Cancer Cells.Antioxidants (Basel, Switzerland) · 2020Article
- Roles of Reactive Oxygen Species in Biological Behaviors of Prostate Cancer.BioMed research international · 2020Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Despite androgen deprivation therapy (ADT), persistent androgen receptor (AR) signaling enables outgrowth of castration resistant prostate cancer (CRPC). In prostate cancer (PCa) cells, ADT may enhance AR activity through induction of oxidative stress. Herein, we investigated the roles of Nrf1 and Nrf2, transcription factors that regulate antioxidant gene expression, on hormone-mediated AR transactivation using a syngeneic in vitro model of androgen dependent (LNCaP) and castration resistant (C4-2B) PCa cells. Dihydrotestosterone (DHT) stimulated transactivation of the androgen response element (ARE) was significantly greater in C4-2B cells than in LNCaP cells. DHT-induced AR transactivation was coupled with higher nuclear translocation of p65-Nrf1 in C4-2B cells, as compared to LNCaP cells. Conversely, DHT stimulation suppressed total Nrf2 levels in C4-2B cells but elevated total Nrf2 levels in LNCaP cells. Interestingly, siRNA mediated silencing of Nrf1 attenuated AR transactivation while p65-Nrf1 overexpression enhanced AR transactivation. Subsequent studies showed that Nrf1 physically interacts with AR and enhances AR's DNA-binding activity, suggesting that the p65-Nrf1 isoform is a potential AR coactivator. In contrast, Nrf2 suppressed AR-mediated transactivation by stimulating the nuclear accumulation of the p120-Nrf1 which suppressed AR transactivation. Quantitative RT-PCR studies further validated the inductive effects of p65-Nrf1 isoform on the androgen regulated genes, PSA and TMPRSS2. Therefore, our findings implicate differential roles of Nrf1 and Nrf2 in regulating AR transactivation in PCa cells. Our findings also indicate that the DHT-stimulated increase in p65-Nrf1 and the simultaneous suppression of both Nrf2 and p120-Nrf1 ultimately facilitates AR transactivation in CRPC cells.
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