ArticleThe Prostate2017
High-Content Screening Identifies Src Family Kinases as Potential Regulators of AR-V7 Expression and Androgen-Independent Cell Growth.
Article in The Prostate, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Androgen receptor variant-driven prostate cancer II: advances in laboratory investigations.Prostate cancer and prostatic diseases · 2020Pooled it
- Randomized Phase II Trial of Abiraterone Alone or With Dasatinib in Men With Metastatic Castration-resistant Prostate Cancer (mCRPC).Clinical genitourinary cancer · 2019Trial
- Oxidative stress reactivates androgen receptor signaling via USP36 to drive castration resistance in prostate cancer.Scientific reports · 2025Article
- Article
- Strategies to Re-Sensitize Castration-Resistant Prostate Cancer to Antiandrogen Therapy.Biomedicines · 2023Review
- Sensitive image-based chromatin binding assays using inducible ERα to rapidly characterize estrogenic chemicals and mixtures.iScience · 2022Article
- Androgen receptor variant-7 regulation by tenascin-c induced src activation.Cell communication and signaling : CCS · 2022Article
- Review
- Maternal Protein Restriction Alters the Expression of Proteins Related to the Structure and Functioning of the Rat Offspring Epididymis in an Age-Dependent Manner.Frontiers in cell and developmental biology · 2022Article
- Regulation and targeting of androgen receptor nuclear localization in castration-resistant prostate cancer.The Journal of clinical investigation · 2021Article
- A Novel Small Molecule Targets Androgen Receptor and Its Splice Variants in Castration-Resistant Prostate Cancer.Molecular cancer therapeutics · 2020Article
- Review
- Down-regulation of AR splice variants through XPO1 suppression contributes to the inhibition of prostate cancer progression.Oncotarget · 2018Article
- Androgen Receptor Could Be a Potential Therapeutic Target in Patients with Advanced Hepatocellular Carcinoma.Cancers · 2017Article
- Current opinion and mechanistic interpretation of combination therapy for castration-resistant prostate cancer.Asian journal of andrologyReview
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAR-V7 is an androgen receptor (AR) splice variant that lacks the ligand-binding domain and is isolated from prostate cancer cell lines. Increased expression of AR-V7 is associated with the transition from hormone-sensitive prostate cancer to more advanced castration-resistant prostate cancer (CRPC). Due to the loss of the ligand-binding domain, AR-V7 is not responsive to traditional AR-targeted therapies, and the mechanisms that regulate AR-V7 are still incompletely understood. Therefore, we aimed to explore existing classes of small molecules that may regulate AR-V7 expression and intracellular localization and their potential therapeutic role in CRPC.
methodsWe used AR high-content analysis (AR-HCA) to characterize the effects of a focused library of well-characterized clinical compounds on AR-V7 expression at the single-cell level in PC3 prostate cancer cells stably expressing green fluorescent protein (GFP)-AR-V7 (GFP-AR-V7:PC3). In parallel, an orthogonal AR-HCA screen of a small interfering (si)RNA library targeting 635 protein kinases was performed in GFP-AR-V7:PC3. The effect of the Src-Abl inhibitor PD 180970 was further characterized using cell-proliferation assays, quantitative PCR, and western blot analysis in multiple hormone-sensitive and CRPC cell lines.
resultsCompounds that tended to target Akt, Abl, and Src family kinases (SFKs) decreased overall AR-V7 expression, nuclear translocation, absolute nuclear level, and/or altered nuclear distribution. We identified 20 protein kinases that, when knocked down, either decreased nuclear GFP-AR-V7 levels or altered AR-V7 nuclear distribution, a set that included the SFKs Src and Fyn. The Src-Abl dual kinase inhibitor PD180970 decreased expression of AR-V7 by greater than 46% and decreased ligand-independent transcription of AR target genes in the 22RV1 human prostate carcinoma cell line. Further, PD180970 inhibited androgen-independent cell proliferation in endogenous-AR-V7-expressing prostate cancer cell lines and also overcame bicalutamide resistance observed in the 22RV1 cell line.
conclusionsSFKs, especially Src and Fyn, may be important upstream regulators of AR-V7 expression and represent promising targets in a subset of CRPCs expressing high levels of AR-V7. Prostate 77:82-93, 2017. © 2016 Wiley Periodicals, Inc.
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