Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Whole Exome-seq profiles of prostate cancer cell lines for copy number and PARADIGM analysis

ABSTRACT: Genomic studies using paired enzalutamide-sensitive and resistant cell models were performed. After transcriptional and copy number profiling, we used PARADIGM to compare the genomic alterations between the parental V16D and resistant MR49F cell models to identify critically deregulated networks to demonstrate the utility of integrative genomic analysis for therapy selection. There were 607 genes and pathway entities that had PARADIGM scores that fell outside the normally distributed range in the MR49F cell line. The top 64 genes were selected for RNAi validation. The most biologically relevant genes between the V16D and MR49F cell line models under enzalutamide treatment conditions were identified as significant by siRNA analysis and deemed biologically relelvant by network and enrichment analyses.

ORGANISM(S): Homo sapiens

PROVIDER: GSE87136 | GEO | 2018/02/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Paradigm Test Set

Project description:Paradigm Test Set

| PRJNA150683 | ENA

Paradigm Test Set

Project description:This SuperSeries is composed of the following subset Series: GSE35186: Paradigm Test Set Expression Array GSE35189: Paradigm Test Set aCGH Array Refer to individual Series

2012-06-20 | E-GEOD-35191 | biostudies-arrayexpress

Cellular androgen content influences enzalutamide agonism of F877L mutant androgen receptor

Project description:Prostate cancer is the most commonly diagnosed and second-most lethal cancer among men in the United States. The vast majority of prostate cancer deaths are due to castration-resistant prostate cancer (CRPC) â?? the lethal form of the disease that has progressed despite therapies that interfere with activation of androgen receptor (AR) signaling. One emergent resistance mechanism to medical castration is synthesis of intratumoral androgens that activate the AR. This insight led to the development of the AR antagonist enzalutamide. However, resistance to enzalutamide invariably develops, and disease progression is nearly universal. One mechanism of resistance to enzalutamide is an F877L mutation in the AR ligand-binding domain that can convert enzalutamide to an agonist of AR activity. However, mechanisms that contribute to the agonist switch had not been fully clarified, and there were no therapies to block AR F877L. Using cell line models of castration-resistant prostate cancer (CRPC), we determined that cellular androgen content influences enzalutamide agonism of mutant F877L AR. Further, enzalutamide treatment of AR F877L-expressing cell lines recapitulated the effects of androgen activation of F877L AR or wild-type AR. Because the BET bromodomain inhibitor JQ-1 was previously shown to block androgen activation of wild-type AR, we tested JQ-1 in AR F877L-expressing CRPC models. We determined that JQ-1 suppressed androgen or enzalutamide activation of mutant F877L AR and suppressed growth of mutant F877L AR CRPC tumors in vivo, demonstrating a new strategy to treat tumors harboring this mutation. RNA-seq profiles of prostate cancer cell lines to understand gene expression associated with enzalutamide treatment

2016-06-10 | E-GEOD-69896 | biostudies-arrayexpress

Linking prostate cancer cell AR heterogeneity to distinct castration and Enzalutamide responses

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

microRNA Expression based, Effects of Chronic Intermittent Ethanol paradigm on mouse brain

2013-12-31 | GSE48576 | GEO

Expression data from prostate cancer cell lines C4-2B (enzalutamide sensitive) and C4-2B-MDVR (enzalutamide resistant) cells

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

microRNA Expression based, Effects of Chronic Intermittent Ethanol paradigm on mouse brain

Project description:We analyzed cerebral cortices (CTX) and midbrains (MB) from male C57BL/6J mice subjected to a CIE, 2BC paradigm, which induces heavy drinking and represents one of the best available animal models for alcohol dependence and relapse drinking. Samples from CTX and MB of 21 mice: 7 Naïve, 7 Air-2BC, and 7 CIE-2BC. One channel was used for the actual sample, the second channel was used fot Internal QC Reference.

2013-12-31 | E-GEOD-48576 | biostudies-arrayexpress

LNCAP/AR and a LnCAP/AR subline (LREX') with acquired resistance to 2nd generation antiandrogens

Project description:The treatment of advanced prostate cancer has been transformed by novel antiandrogen therapies such as enzalutamide. Using the LnCaP/AR xenograft model, we identified induction of glucocorticoid receptor (GR) expression as a common feature of drug resistant tumors. From a resistant xenograft tumor, we derived a GR expressing resistant subline called LREX' which maintains the resistant phenotype. mRNA expression was used to characterize resistant tissues. LnCaP/AR cells were injected into castrate mice and tumors were established. Mice were then treated with vehicle (Con), 4 days of anti-androgen (ARN-509 10mgkg), or were maintained on anti-androgen (10mg/kg ARN-509 or enzalutamide) until emergence of resistance. Resistant tissues continued to be exposed to anti-androgen through time of harvest. LREX' (LnCaP/AR Resistant to Enzalutamide Xenograft Derived) was derived from an enzalutamide resistant xenograft and was re-injected into castrate mice undergoing continual treatment with enzalutamide. The GR probe on the Illumina array failed to detect GR expression. Therefore, GR expression as determined by qPCR is annotated separately. Of the 10 control tissues, 8 were analyzed twice (technical duplicates annotated as A and B).

2013-12-27 | E-GEOD-51873 | biostudies-arrayexpress

Patient Derived Xenograft for Delivery of Precision Medicine in Castrate Resistant Prostate Cancer

Project description:Developing animal models representating the cancer biology of advanced prostate cancer patients is challenging but essential for delivering individualized medical therapies. In an effort to develop patient derived xenograft (PDX) models, we took the metastatic site tissue from the rib lesion twice (ie, before and after enzalutamide treatment) over a twelve week period and implanted subcutaneously and under the renal capsule in immuno-deficient mice. To characterize and compare the genome and transcriptome landscapes of patient tumor tissues and the corresponding PDX models, we performed whole exome and transcriptome sequencing for metastatic tumor tissue as well as its derived PDXs. We demonstrated the feasibility of developping PDX models from patient who developed castrate-resistant prostate cancer. Our data suggested PDX models preserve the patient’s genomic and transcriptomic alterations in high fidelity, as illustrated by somatic mutation, copy number variation, gene fusion and gene expression. RNA sequencing of prostate cancer tumor tissue and derived xenograft using Illumina HiSeq 2000.

2015-06-30 | E-GEOD-70380 | biostudies-arrayexpress

Paradigm Test Set aCGH Array

Project description:aCGH data was used in Paradigm analysis for exploration of networks affected by copy number and gene expression changes based on mutation spectra of recurrently mutated genes in breast cancer.

2012-06-21 | GSE35189 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data