Gene expression profiling study of VCaP xenograft tumors collected from intact and castrated athymic nude mice
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE56829 | GEO | 2014/04/21
SECONDARY ACCESSION(S): PRJNA244699
REPOSITORIES: GEO
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Project description:The purpose of the study was to characterize the properties of human prostate cancer VCaP tumors pre- and post-castration. The main focus was on androgen signaling, androgen metabolism and steroid synthesis. Results provide valuable information about how castration-resistant tumors (CRPC) are able grow in absence of gonadal androgens. One million VCaP cells were inoculated orthotopically into the dorsolateral prostate of nude mice through an abdominal incision. Tumor growth was followed by serum PSA measurements. Intact mice were sacrificed and tumors were collected 3-14 weeks after inoculation (Intact 1, Intact 2). Mice in the remaining three groups (GNX, CRPC 1, CRPC 2) were castrated by removing the testes. Mice were sacrificed and tumors were collected one day after castration (GNX) or 3-14 weeks after castration (CRPC 1, CRPC 2) in castration-resistant stage. 4 tumors were selected from each study group, totally 20 tumors.
2014-04-21 | E-GEOD-56829 | biostudies-arrayexpress
Project description:Through comparative genomics using PDX models of androgen-dependent (AD) and castration-resistant (CR) tumors, we identify opioid receptor kappa 1 (OPRK1) as being associated with castration-resistance. Loss of OPRK1 function delays castration-resistance and inhibits castration-resistant growth of prostate cancer cells in culture and in vivo, suggesting OPRK1 as a therapeutic target. To gain insight with regard to biological function of OPRK1 under androgen-depleted condition, we set up two distinct comparisons using VCaP and AIVCaP cells. AIVCaP is an androgen-independent subline of VCaP which we established. VCaP or AIVCaP were treated with siRNA for AR plus siRNA for OPRK1 (combo-siRNA) or siRNA for AR alone (single siRNA) (n = 4 each), and then expression profile gained from microarray analysis of the respective cell line treated with combo-siRNA was compared with that of cells treated with single siRNA.
2022-04-03 | GSE194248 | GEO
Project description:We report RNA sequencing data on serial biopsies of prostate cancer VCaP xenografts as the tumors pass from androgen-sensitivity (Pre-Cx), to castration resistance (CRPC, castration resistant prostate cancer), onto resistance to dual therapy with abiraterone plus enzalutamide (AER). From comparison of these RNAseq data sets, we were able to determine differentially expressed genes between the AER/CRPC and Pre-Cx states that could mediate resistance to androgen deprivation therapies.
2018-12-26 | GSE109708 | GEO
Project description:Here, we analyze gene expression of prostate cancer cell line VCaP (VCaP WT) and VCaP after testosterone boost (VCaPrev) in order to investigate the impact of the androgen axis on susceptibility to PCA treatments which are not directly AR-directed.
2020-12-31 | GSE159531 | GEO
Project description:Purpose: Monoamine oxidase A (MAOA) is a mitochondrial enzyme that degrades neurotransmitters including serotonin and norepinephrine. Its inhibitors are commonly used to treat neurologic conditions including depression. Recently, we and others identified high expression of MAOA in normal basal prostate epithelium and in high grade primary prostate cancer (PCa). Inhibition of MAOA with an irreversible inhibitor, clorgyline, induced differentiation in primary cultures of epithelial cells from normal tissues and high grade cancers. Furthermore, clorgyline treatment inhibited several oncogenic pathways in PCa cells, suggesting a clinical value of MAOA inhibitors as a pro-differentiation and anti-oncogenic therapy for high risk PCa. Here, we extended our studies to a model of advanced PCa, VCaP cells, which were derived from castration-resistant metastatic PCa and express a high level of MAOA. Methods: The growth of VCaP cells in the presence or absence of clorgyline was evaluated in vitro and in vivo. Gene expression changes in response to clorgyline were determined by microarray and validated by quantitative real-time PCR. Results: Treatment with clorgyline in vitro inhibited growth and altered the transcriptional pattern of VCaP cells in a manner consistent with the pro-differentiation and anti-oncogenic effects seen in treated primary PCa cells. Src, beta-catenin, and MAPK oncogenic pathways, implicated in androgen-independent growth and metastasis, were significantly downregulated. Clorgyline treatment of mice bearing VCaP xenografts slowed tumor growth and induced transcriptome changes similar to those noted in vitro. Conclusions: Our results support the possibility that anti-depressant drugs that target MAOA might find a new application in treating PCa. Compound Based Treatment: Clorgyline treament of VCaP cells compound_treatment_design
2010-10-25 | E-GEOD-19822 | biostudies-arrayexpress
Project description:Microarray experiments were performed for VCaP and VCS2 cells with and without androgen stimulation
2012-02-01 | GSE32344 | GEO
Project description:Purpose: Monoamine oxidase A (MAOA) is a mitochondrial enzyme that degrades neurotransmitters including serotonin and norepinephrine. Its inhibitors are commonly used to treat neurologic conditions including depression. Recently, we and others identified high expression of MAOA in normal basal prostate epithelium and in high grade primary prostate cancer (PCa). Inhibition of MAOA with an irreversible inhibitor, clorgyline, induced differentiation in primary cultures of epithelial cells from normal tissues and high grade cancers. Furthermore, clorgyline treatment inhibited several oncogenic pathways in PCa cells, suggesting a clinical value of MAOA inhibitors as a pro-differentiation and anti-oncogenic therapy for high risk PCa. Here, we extended our studies to a model of advanced PCa, VCaP cells, which were derived from castration-resistant metastatic PCa and express a high level of MAOA. Methods: The growth of VCaP cells in the presence or absence of clorgyline was evaluated in vitro and in vivo. Gene expression changes in response to clorgyline were determined by microarray and validated by quantitative real-time PCR. Results: Treatment with clorgyline in vitro inhibited growth and altered the transcriptional pattern of VCaP cells in a manner consistent with the pro-differentiation and anti-oncogenic effects seen in treated primary PCa cells. Src, beta-catenin, and MAPK oncogenic pathways, implicated in androgen-independent growth and metastasis, were significantly downregulated. Clorgyline treatment of mice bearing VCaP xenografts slowed tumor growth and induced transcriptome changes similar to those noted in vitro. Conclusions: Our results support the possibility that anti-depressant drugs that target MAOA might find a new application in treating PCa. Compound Based Treatment: Clorgyline treament of VCaP cells
2010-10-25 | GSE19822 | GEO
Project description:Androgen receptor (AR) is typically overexpressed in castration-resistant prostate cancer (CRPC). CRPC-derived VCaP cells display an excessive number of chromatin AR-binding sites (ARBs). This study analyzed direct transcription programs of the AR, the prevalence of AR enhancers and the transcriptional regulators involved in the regulation of at the enhancer regions. The analysis utilized global nuclear run-on sequencing (GRO-seq). The GRO-seq data were integrated with the ARB and VCaP cell-specific transcription factor-binding data. Androgen in 30 min activated and repressed transcription of a large number of genes including novel AR targets IGF-1 receptor and EGF receptor. GRO-seq analysis also revealed that only a fraction of the ARBs resides at functional enhancers. Activation of AR bound enhancers was most potent at the sites that also bound PIAS1, ERG and HDAC3. Our genome-wide data provide new insights how AR can directly control growth-signaling pathways in CPRC cells.
2016-10-06 | GSE84432 | GEO
Project description:Microarray experiments were performed for VCaP and VCS2 cells with and without androgen stimulation The RNA samples were extracted from VCaP and VCS2 cells treated with Ethanol or 10nM DHT for 24 hours. RNA was submitted to Dana-Farber Cancer Institute Microarray Core Facility for hybridyzation.
2012-02-01 | E-GEOD-32344 | biostudies-arrayexpress
Project description:Molecular mechanisms underlying resistance to androgen deprivation therapy (ADT) and, in particular, to antiandrogen Enzalutamide, in treating castration-resistant prostate cancer (CRPC), remain incompletely understood. Through screening >120 CRPC patient samples, we observed 3 expression patterns of androgen receptor (AR) protein: primarily nuclear (nuc-AR), mixed nuclear/cytoplasmic expression (nuc/cyto-AR), and low/no expression (AR-/lo). Xenograft CRPC modeling in 4 models (i.e., LNCaP, VCaP, LAPC4, and LAPC9) recapitulated the 3 AR expression patterns in castration-resistant tumors developed from parental androgen-dependent tumors. Strikingly, although the 3 CRPC models that retained AR expression (LNCaP, VCaP, and LAPC4) responded, to different levels and in different kinetics, to Enzalutamide, the AR-/lo LAPC9 CRPC was completely refractory to Enzalutamide. By combining whole-genome RNA-Seq and biochemical analyses together with experimental combinatorial therapy in the LNCaP and LAPC9 models, we identified BCL-2 as a critical therapeutic target in both AR+/hi and AR-/lo, Enzalutamide-resistant CRPC models.
2018-08-01 | GSE88752 | GEO