Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA117241 | ENA |
REPOSITORIES: ENA
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Project description:The ligand-activated androgen receptor is a transcription factor that drives prostate cancer growth. Blocking androgen-activation of androgen receptor via androgen deprivation therapy is the default treatment for metastatic prostate cancer. Despite initial remissions, androgen deprivation invariably fails and prostate cancer progresses to castration-recurrent disease, which still relies on aberrantly activated androgen receptor. Alternative approaches are needed to inhibit androgen receptor action in prostate cancer that has failed androgen deprivation therapy. Our laboratory has been exploring the therapeutic potential of a non-canonical androgen receptor signaling mechanism wherein androgen receptor stimulates another transcription factor, Serum Response Factor. Serum Response Factor-mediated androgen receptor action correlates with prostate cancer progression and is enriched in castration-recurrent prostate cancer. Inhibiting Serum Response Factor-dependent androgen receptor action may be an effective treatment strategy following failure of androgen deprivation therapy but remains poorly understood. We have recently isolated UPF1 and RCOR1 as putative novel mediators of Serum Response Factor-dependent androgen receptor action. Here, we perform RNA-Seq assays to determine the contribution of UPF1 and RCOR1 to the androgen response of prostate cancer cells.
2025-05-15 | GSE248034 | GEO
Project description:Progression to androgen independent is the main cause of death in prostate cancer, and the mechanism is still unclear. By reviewing the expression profiles of 26 prostate cancer samples in a holistic view, we found a group of genes differentially expressed in androgen independent compared with androgen dependent groups (p value< 0.01, t test). Focusing on apoptosis, proliferation, hormone and angiogenesis, we found a group of genes such as thioredoxin domain containing 5 (TXNDC5), tumor necrosis factor receptor superfamily, member 10a (TNFRSF10A), ribosomal protein S19 (RPS19) and Janus kinase 2 (JAK2) up-regulated in androgen independent prostate cancer, which could play important roles in the transition from androgen dependent to androgen independent and could be biomarkers of prognosis. The main aim was comparing the androgen dependent and androgen independent prostate cancer to identify differentially expressed genes. In addition, we added several normal prostate tissue sample for comparisons. Totally 29 experiments were performed without replicates. 3 for normal prostate tissue, 8 for androgen independent cancer and 18 for androgen dependent prostate cancer. In all experiments, the reference samples are common reference, a pool with unrelated fetal tissues.
2007-09-09 | E-GEOD-5803 | biostudies-arrayexpress
Project description:Abstract Background. The cellular effects of androgen are transduced through the androgen receptor, which controls the expression of genes that regulate biosynthetic processes, cell growth, and metabolism. Androgen signaling also impacts DNA damage signaling through mechanisms involving gene expression and transcription-associated DNA damaging events. Defining the contributions of androgen signaling to DNA repair is important for understanding androgen receptor function, and it also has important translational implications. Methods. We generated RNA-seq data from multiple prostate cancer lines and used bioinformatic analyses to characterize androgen-regulated gene expression. We compared the results from cell lines with gene expression data from prostate cancer xenografts, and patient samples, to query how androgen signaling and prostate cancer progression influences the expression of DNA repair genes. We performed whole genome sequencing to help characterize the status of the DNA repair machinery in widely used prostate cancer lines. Finally, we tested a DNA repair enzyme inhibitor for effects on androgen-dependent transcription. Results. Our data indicates that androgen signaling regulates a subset of DNA repair genes that are largely specific to the respective model system and disease state. We identified deleterious mutations in the DNA repair genes RAD50 and CHEK2. We found that inhibition of the DNA repair enzyme MRE11 with the small molecule mirin inhibits androgen-dependent transcription and growth of prostate cancer cells. Conclusions. Our data supports the view that crosstalk between androgen signaling and DNA repair occurs at multiple levels, and that DNA repair enzymes in addition to PARPs, could be actionable targets in prostate cancer.
2018-09-30 | GSE120660 | GEO
Project description:To investigate the mechanisms of drug resistance and castration resistance in prostate cancer, we performed proteomic sequencing on androgen-dependent prostate cancer cells (LNCaP) and androgen-independent cells (AI) treated with enzalutamide.
2024-11-26 | PXD058261 |
Project description:Androgen receptor (AR) is a ligand-dependent transcription factor that plays a key role in the onset and progression of prostate cancer. We investigated AR-induced gene expression in prostate cancer cells LNCaP and abl by transfecting siAR / siControl or treating cells with androgen (DHT) over a time course. Experiment Overall Design: We hybridized RNA to Affymetrix human genome U133 plus 2.0 arrays.
2009-08-07 | E-GEOD-11428 | biostudies-arrayexpress
Project description:In castration-resistant prostate cancer (CRPC), clinical response to androgen receptor (AR) antagonists is limited mainly due to AR-variants expression and restored AR signaling. The metabolite spermine is most abundant in prostate and it decreases as prostate cancer progresses, but its functions remain poorly understood. Here, we show spermine inhibits full-length androgen receptor (AR-FL) and androgen receptor splice variant 7 (AR-V7) signaling and suppresses CRPC cell proliferation by directly binding and inhibiting protein arginine methyltransferase PRMT1. Spermine reduces H4R3me2a modification at the AR locus and suppresses AR binding as well as H3K27ac modification levels at AR target genes. Spermine supplementation restrains CRPC growth in vivo. PRMT1 inhibition also suppresses AR-FL and AR-V7 signaling and reduces CRPC growth. Collectively, we demonstrate spermine as an anticancer metabolite by inhibiting PRMT1 to transcriptionally inhibit AR-FL and AR-V7 signaling in CRPC, and we indicate spermine and PRMT1 inhibition as powerful strategies overcoming limitations of current AR-based therapies in CRPC.
2023-10-11 | MTBLS8034 | MetaboLights
Project description:We analyzed mutations in Epidermal Growth Factor Receptor (EGFR) Tyrosine kinase (TK) domain, EGFR expression and gene profiling in prostate carcinoma (PC) in order to find out molecular prognostic markers and supply a proof for EGFR targeted therapies. 100 glyofixx-fixed, paraffin-embedded PC specimens were recovered after radical prostatectomy from locally advanced PC patients. Exons from 18 to 21 of EGFR TK domain were amplified and sequenced. For the entire cohort, EGFR protein evaluation by immunohistochemistry was performed. Gene expression profile was analyzed on 51 out of 100 samples by whole genome microarray. Statistical tests were performed in order to detect any significant association between EGFR iperexpression and prognosis. None out of 100 specimens presented mutations in exon 18; 2 point mutations were identified in exon 19, 5 in exon 20 and 6 in exon 21. In addiction, 58 out of 100 patients had the same silent mutation, at codon 787 in exon 20. EGFR iper-expression was found in 36% of specimens and was significantly associated with biochemical relapse. Gene profiling analysis on mutated samples selected 29 modulated genes differentially expressed between mutated EGFR+ and mutated EGFR- samples; 4 down-regulated genes, EAF2, ABCC4, KLK3 and ANXA3 and one up-regulated gene, FOXC1, are involved in prostate cancer progression. Our findings suggest that a subgroup of PC patients could potentially benefit of EGFR targeted therapies. The EGFR protein evaluation could contribute to identify PC relapsers. Keywords: EGFR expression, TK mutations, target therapy, microarray data. In this work we studied mutation status and expression of Epidermal Growth Factor Receptor (EGFR) in a case series of 100 primary prostate cancer tissue specimens. Results indicate that 13% and 36% of PC patients presents EGFR tyrosine kinase domain mutations and iperexpression respectively, suggesting that this receptor could be a therapeutic target in progressive prostate cancer. The analysis of correlation between EGFR protein expression, mutations, clinical parameters and outcome allow us to identify EGFR as significantly associated with biochemical relapse and high Gleason score. Gene expression profiling in 51 of PC tissues led to the identification of a gene list which separated EGFR mutated patients according to EGFR protein expression. These results could give more information on clinical outcome and possible development of new targeted therapies.
2011-06-30 | E-GEOD-16120 | biostudies-arrayexpress
Project description:The androgen receptor (AR) is a ligand-inducible transcription factor that mediates androgen action in target tissues. Upon ligand binding, the AR binds to thousands of genomic loci and activates a cell-type specific gene program. Prostate cancer growth and progression depend on androgen-induced AR signalling. Treatment of advanced prostate cancer through medical or surgical castration leads to initial response and durable remission, but resistance inevitably develops. In castration-resistant prostate cancer (CRPC), AR activity remains critical for tumor growth despite androgen deprivation. While previous studies have focused on ligand-dependent AR signalling, in this study we explore AR function under the androgen-deprived conditions characteristic of CRPC. Our data demonstrate that the AR persistently occupies a distinct set of genomic loci after androgen deprivation in CRPC. These androgen-independent AR occupied regions have constitutively open chromatin structures that lack the canonical androgen response element and are independent of FoxA1, a transcription factor involved in ligand-dependent AR targeting. Many AR binding events occur at proximal promoters, which can act as enhancers to augment transcriptional activities of other promoters through DNA looping. We further show that androgen-independent AR binding directs a distinct gene expression program in CRPC, which is necessary for the growth of CRPC after androgen withdrawal.
2012-10-02 | GSE40050 | GEO
Project description:The androgen receptor (AR) is a ligand-inducible transcription factor that mediates androgen action in target tissues. Upon ligand binding, the AR binds to thousands of genomic loci and activates a cell-type specific gene program. Prostate cancer growth and progression depend on androgen-induced AR signalling. Treatment of advanced prostate cancer through medical or surgical castration leads to initial response and durable remission, but resistance inevitably develops. In castration-resistant prostate cancer (CRPC), AR activity remains critical for tumor growth despite androgen deprivation. While previous studies have focused on ligand-dependent AR signalling, in this study we explore AR function under the androgen-deprived conditions characteristic of CRPC. Our data demonstrate that the AR persistently occupies a distinct set of genomic loci after androgen deprivation in CRPC. These androgen-independent AR occupied regions have constitutively open chromatin structures that lack the canonical androgen response element and are independent of FoxA1, a transcription factor involved in ligand-dependent AR targeting. Many AR binding events occur at proximal promoters, which can act as enhancers to augment transcriptional activities of other promoters through DNA looping. We further show that androgen-independent AR binding directs a distinct gene expression program in CRPC, which is necessary for the growth of CRPC after androgen withdrawal. LNCaP, C4-2B, or 22RV1 cells were cultured in hormone-free media for 3 days and then treated with ethanol vehicle or DHT (10nM) for 4h or 16h prior to ChIP-seq or RNA-seq assays. For siRNA transfection, cells were transfected with AR siRNA or control siRNA for 3 days prior to RNA-seq assays.
2012-10-02 | E-GEOD-40050 | biostudies-arrayexpress
Project description:Androgen receptor (AR) belongs to a nuclear receptor superfamily and functions as a ligand-dependent transcription factor. AR-regulated transcriptional program is associated with various diseases, especially prostate cancer. Suppression of AR is an effective therapy for AR-dependent prostate cancer. However, in most of the cases it relapses as castration-resistant prostate cancer (CRPC), acquiring resistance to hormone therapy. We investigated the effect of androgen treatment and AR knockdown on gene expression by RNA-seq using CRPC model cells.
2020-06-27 | GSE141806 | GEO