Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA270246 | ENA |
REPOSITORIES: ENA
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Project description:Prostate cancer C4-2B cells were cultured in enzalutamide in a dose-escalation manner. After sixty passages cells were resistant to enzalutamide, with a specific sets of genes been deregulated. We performed global gene expression analysis by cDNA microarrays to identify genes responsible for enzalutamide resistance in C4-2B-MDVR cells. Enzalutamide resistant C4-2B-MDVR cells were selected from C4-2B cells during long time enzalutamide treatment. Genes responsible for enzalutamide resistance were identified using C4-2B vs. C4-2B-MDVR RNA extraction and hybridization on Affymetrix microarrays.
2015-04-09 | E-GEOD-64143 | biostudies-arrayexpress
Project description:We established an enzalutamide-resistant C4-2b prostate cell line that has an active androgen receptor by maintaining the C4-2b cell line in serially increasing concentrations of enzalutamide. Among the CRPC cell lines, we selected the C4-2b cell line because it is known to have AR variants, and we desired to identify enzymes with the ability to regulate the activity of AR variants as well as the wild type AR. After 2 months, we acquired resistant cells in even 10 uM enzalutamide. After validation of enzalutamide-resistant character, we analyzed global changes in mRNA expression by using quantitative mRNA-sequencing analysis.
2020-02-01 | GSE110802 | GEO
Project description:The overall goal of this study was to identify genes differentially expressed in enzalutamide-sensitive (C4-2B Con) and enzalutamide-resistant (C4-2B ENZR) C4-2B cells.
2020-10-20 | GSE159548 | GEO
Project description:Prostate cancer C4-2B cells were cultured in enzalutamide in a dose-escalation manner. After sixty passages cells were resistant to enzalutamide, with a specific sets of genes been deregulated. We performed global gene expression analysis by cDNA microarrays to identify genes responsible for enzalutamide resistance in C4-2B-MDVR cells.
2015-04-09 | GSE64143 | GEO
Project description:Prostate cancer is the second leading cause of cancer death among men in the United States. The androgen receptor (AR) antagonist enzalutamide is a FDA-approved drug for treatment of patients with late-stage prostate cancer and is currently under clinical study for early-stage prostate cancer treatment. After a short positive response period to enzalutamide, tumors will develop drug resistance. In this study, we uncovered that DNA methylation was deregulated in enzalutamide-resistant cells. DNMT activity and DNMT3B expression were upregulated in resistant cell lines. Enzalutamide induced the expression of DNMT3A and DNMT3B in prostate cancer cells with a potential role of p53 and pRB in this process. The overexpression of DNMT3B3, a DNMT3B variant, promoted an enzalutamide-resistant phenotype in C4-2B cell lines. Inhibition of DNA methylation and DNMT3B knockdown induced a re-sensitization to enzalutamide. Decitabine treatment in enzalutamide-resistant cells induced a decrease of the expression of AR-V7 and changes of genes for apoptosis, DNA repair and mRNA splicing. Combination treatment of Decitabine and enzalutamide induced a decrease of tumor weight, Ki-67 and AR-V7 expression and an increase of cleaved-caspase3 levels in 22Rv1 xenografts. The collective results suggest that DNA methylation pathway is deregulated after enzalutamide resistance onset and that targeting DNA methyltransferases restores the sensitivity to enzalutamide in prostate cancer cells.
2021-09-22 | GSE184168 | GEO
Project description:Acquisition of resistance to the PARP inhibitor, Olaparib, constitutes a major challenge for the treatment of advanced prostate cancer. The purpose of this study was to identify molecular targets responsible for the development of acquired Olaparib resistance in advanced prostate cancer. Towards this goal, next-generation sequencing (NGS)-based gene expression profiling (RNA-Sequencing; RNA-Seq) was performed on castration-sensitive prostate cancer (CSPC)/Olaparib-sensitive LNCaP cells, castration-sensitive prostate cancer (CSPC)/Olaparib-resistant LN-OlapR cells, castration-resistant prostate cancer (CSPC)/Olaparib-sensitive C4-2B cells, and castration-resistant prostate cancer (CSPC)/Olaparib-resistant 2B-OlapR cells.
2023-12-06 | GSE249514 | GEO
Project description:To explore the gene regulatory mechanisms underlying PTUPB treatment in drug-resistant prostate cancer cells. We performed RNA sequencing analyses using PTUPB-treated C4-2B MDVR cells with or without enzalutamide treatment to identify the gene programs affected by the treatments.
2022-11-02 | GSE216777 | GEO
Project description:The androgen receptor (AR) is overexpressed and hyperactivated in human castration-resistant prostate cancer (CRPC). However, the determinants of AR overexpression in CRPC are poorly defined. Here we show that retinoic acid receptorârelated orphan receptor γ (ROR-γ) is overexpressed and amplified in metastatic CRPC tumors, and that ROR-γ drives AR expression in the tumors. ROR-γ recruits nuclear receptor coactivator 1 and 3 (NCOA1 and NCOA3, also known as SRC-1 and SRC-3) to an ARâROR response element (RORE) to stimulate AR gene transcription. ROR-γ antagonists suppress the expression of both AR and its variant AR-V7 in prostate cancer (PCa) cell lines and tumors. ROR-γ antagonists also markedly diminish genome-wide AR binding, H3K27ac abundance and expression of the AR target gene network. Finally, ROR-γ antagonists suppressed tumor growth in multiple AR-expressing, but not AR-negative, xenograft PCa models, and they effectively sensitized CRPC tumors to enzalutamide, without overt toxicity in mice. Taken together, these results establish ROR-γ as a key player in CRPC by acting upstream of AR and as a potential therapeutic target for advanced PCa. A total of 6 samples were analyzed in this study. The study included one cell line C4-2B. C4-2B cells were cultured in medium containing vehicle control and/or SR2211 and/or XY011 and/or Enzalutamide (ENZ). The untreated C4-2B cells served as controls for the study.
2016-03-08 | E-GEOD-72483 | biostudies-arrayexpress
Project description:Expression data from prostate cancer cell lines C4-2B (docetaxel sensitive) and TaxR (docetaxel resistant) cells
| PRJNA203356 | ENA
Project description:The goal of this analysis is to profile AR-regulated genes, especially non-coding RNAs in three androgen sensitive prostate cancer cell lines, MDA-PCA-2B, LNCaP and VCaP. The two cell lines were serum-starved first, followed by dihydrotestosterone (DHT) stimulation or treated with Enzalutamide (AR inhibitor) without starvation. Transcriptome profiling was generated by RNA-sequencing from polyA-selected RNA. These experiments are followed by knock-down experiments of AR and ARlnc1 in MDA-PCA-2B, and also Enzalutamide (anti-androgen) treatment of LNCaP cells.
2018-02-21 | GSE110903 | GEO