ArticleThe international journal of biochemistry & cell biology2013
Targeted disruption of the p160 coactivator interface of androgen receptor (AR) selectively inhibits AR activity in both androgen-dependent and castration-resistant AR-expressing prostate cancer cells.
Article in The international journal of biochemistry & cell biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Androgen Receptor-Interacting Proteins in Prostate Cancer Development and Therapy Resistance.The American journal of pathology · 2024Review
- Evaluation of AR, AR-V7, and p160 family as biomarkers for prostate cancer: insights into the clinical significance and disease progression.Journal of cancer research and clinical oncology · 2024Article
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- Characterization of allosteric modulators that disrupt androgen receptor co-activator protein-protein interactions to alter transactivation-Drug leads for metastatic castration resistant prostate cancer.SLAS discovery : advancing life sciences R & D · 2023Article
- Review
- Cistrome and transcriptome analysis identifies unique androgen receptor (AR) and AR-V7 splice variant chromatin binding and transcriptional activities.Scientific reports · 2022Article
- Identification of evodiamine as a suppressor of prostate cancer progression by reducing AR transcriptional activity via targeting Src.Endocrine · 2022Article
- Epigenetic Coregulation of Androgen Receptor Signaling.Advances in experimental medicine and biology · 2022Article
- A Review of the Pathophysiological Mechanisms Underlying Castration-resistant Prostate Cancer.Research and reports in urology · 2021Review
- TXNDC9 regulates oxidative stress-induced androgen receptor signaling to promote prostate cancer progression.Oncogene · 2020Article
- Steroid receptor/coactivator binding inhibitors: An update.Molecular and cellular endocrinology · 2019Review
- High Content Positional Biosensor Assay to Screen for Compounds that Prevent or Disrupt Androgen Receptor and Transcription Intermediary Factor 2 Protein-Protein Interactions.Methods in molecular biology (Clifton, N.J.) · 2018Article
- Targeting AR Variant-Coactivator Interactions to Exploit Prostate Cancer Vulnerabilities.Molecular cancer research : MCR · 2017Article
- Epigenomic Regulation of Androgen Receptor Signaling: Potential Role in Prostate Cancer Therapy.Cancers · 2017Review
- Reconfiguring the AR-TIF2 Protein-Protein Interaction HCS Assay in Prostate Cancer Cells and Characterizing the Hits from a LOPAC Screen.Assay and drug development technologies · 2016Article
- Moving Beyond the Androgen Receptor (AR): Targeting AR-Interacting Proteins to Treat Prostate Cancer.Hormones & cancer · 2016Review
- Identification of a Novel Coregulator, SH3YL1, That Interacts With the Androgen Receptor N-Terminus.Molecular endocrinology (Baltimore, Md.) · 2015Article
- Mechanisms of drug resistance that target the androgen axis in castration resistant prostate cancer (CRPC).The Journal of steroid biochemistry and molecular biology · 2015Review
- miR-137 Targets p160 Steroid Receptor Coactivators SRC1, SRC2, and SRC3 and Inhibits Cell Proliferation.Molecular endocrinology (Baltimore, Md.) · 2015Article
- The AhR Ligand, TCDD, Regulates Androgen Receptor Activity Differently in Androgen-Sensitive versus Castration-Resistant Human Prostate Cancer Cells.International journal of environmental research and public health · 2015Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The evidence that androgen blockade-resistant prostate cancer, termed castration resistant, remains androgen receptor (AR) dependent is compelling. AR is re-activated through multiple mechanisms including expression of constitutively active splice variants that lack hormone binding domains (HBDs). This highlights the need to develop therapies that target regions other than the HBD. Because the p160 coactivators interact most strongly with the amino-terminus of AR, we examined the consequences of disrupting this interaction. We identified two overlapping SRC-1 peptides that interact with AR, but not with progesterone receptor. These peptides reduce AR and AR variant AR-V7 dependent induction of an AR responsive reporter. Using mammalian two hybrid assays, we found that the peptides interrupt the AR/SRC-1, AR/SRC-2 and AR N/C interactions, but not SRC-1/CARM-1 interactions. Consistent with the SRC-1 dependence of induced, but not repressed genes, in LNCaP cells, the peptides inhibited hormone dependent induction of endogenous target genes including PSA and TMPRSS2, but did not block AR dependent repression of UGT2B17 or inhibit vitamin D receptor activity. Simultaneous detection of SRC-1 peptides and PSA by double immunofluorescence in transfected LNCaP cells clearly demonstrated a strong reduction in PSA levels in cells expressing the peptides. The peptides also inhibited the AR dependent expression of PSA in castration resistant C4-2 cells. Moreover they inhibited androgen dependent proliferation of LNCaP cells and proliferation of C4-2 cells in androgen depleted medium without affecting AR negative PC-3 cells. Thus, the p160 coactivator binding site is a novel potential therapeutic target to inhibit AR activity.
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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.