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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Global gene expression analysis in macrophages treated with Nutlin-3

ABSTRACT: The goal of the study is to identify p53 target genes specific to macrophages using the p53 stabilizer, Nutlin-3. Macrophages were differentiated x-vivo from monocytes obtained from healthy volunteers either left untreated or treated for 2 hours with 100 ng/mL of lipopolysaccharide (LPS), 0.1%v/v of DMSO (vehicle control for Nutlin-3) or 10 micromolar Nutlin-3. Three replicates were included for each treatment group.

ORGANISM(S): Homo sapiens

SUBMITTER: NIEHS Microarray Core

PROVIDER: E-GEOD-43596 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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p53 and NF-κB coregulate proinflammatory gene responses in human macrophages.

Lowe Julie M JM Menendez Daniel D Bushel Pierre R PR Shatz Maria M Kirk Erin L EL Troester Melissa A MA Garantziotis Stavros S Fessler Michael B MB Resnick Michael A MA

Cancer research 20140401 8

Macrophages are sentinel immune cells that survey the tissue microenvironment, releasing cytokines in response to both exogenous insults and endogenous events such as tumorigenesis. Macrophages mediate tumor surveillance and therapy-induced tumor regression; however, tumor-associated macrophages (TAM) and their products may also promote tumor progression. Whereas NF-κB is prominent in macrophage-initiated inflammatory responses, little is known about the role of p53 in macrophage responses to en ...[more]

PMID: 24737129

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Global gene expression analysis in macrophages treated with Nutlin-3

Project description:The goal of the study is to identify p53 target genes specific to macrophages using the p53 stabilizer, Nutlin-3.

2014-05-21 | GSE43596 | GEO

MicroRNA profiling by array of human multiple myloma p53 wild type cells treated with nutlin 3A

Project description:The miRNA profiles were analyzed for nutlin 3A treated and untreated multiple myloma p53 wild type cells

2010-07-22 | E-TABM-1038 | biostudies-arrayexpress

Expression data from human sarcoma patient samples treated with either vehicle control or Nutlin-3a

Project description:This study has examined the molecular mechanisms underlying sensitivity of sarcomas to Nutlin-3a, a non-genotoxic activator of the p53 pathway. Human patient material was collected immediately following surgical resection, dissected into small pieces and ex planted onto gelatin sponges immersed in media containing either vehicle control or Nutlin-3a (10uM and/or 50uM) for 48 hours. Nutlin-3a represents a novel targeted therapy for the treatment of sarcomas. We have examined expression profiles of genes upregulated in sarcoma patient derived tissues following nutlin-3a treatment ex vivo 16 samples ((Vehicle control and Nutlin-3a (10uM and 50uM) treated samples)) from 6 sarcoma patients

2014-03-10 | E-GEOD-48296 | biostudies-arrayexpress

Genome-wide map of p53 binding sites by ChIP-seq in human lymphoblastoid cell lines treated with nutlin-3

Project description:We have used chromatin immune-precipitation with parallel sequencing (ChIP-Seq) technology to identify genome-wide p53 binding in human lymphoblastoid cell lines treated with a MDM2 inhibitor nutlin-3 ChIP-Seq analysis of p53 binding sites in human lymphoblastoid cells treated with nutlin-3 or vehicle

2013-10-23 | E-GEOD-46992 | biostudies-arrayexpress

HCT116 cells isogenic for p53 expression upon treatment with actinomycin D and nutlin-3

Project description:HCT116 wild type cells express p53. The isogenic HCT116 p53KO cells have the p53 gene knocked out. Cells were treated for 16 hours. Dosages for actinomycin D treatment was 1 nM, 10 nM, and 100 nM. Dosage for nutlin-3 was 4 uM. Keywords: dose response Measuring the gene expression profile of the isogenic cell lines when the cells were treated with 2 different drugs at different concentrations

2010-06-24 | E-GEOD-12459 | biostudies-arrayexpress

Expression data of A375 melanoma cells after DMSO or MLN4924 +/- Nutlin treatment for 26 hours

Project description:Microarrays were used to determine the change in gene expression of genes involved in the p53 pathway after siRNA knock down of p53, CDT1 or BRCA1 A375 cells were grown, transfected with siRNA, incubated for 48hrs, then incubated for another 26hrs in the presence of either 0.065% DMSO as control, 650nM MLN4924, 5uM Nutlin or 100nM Daunorubicin. RNA extraction and hybridization on Affymetrix HG-U133Plus 2.0 arrays were performed. 12 conditions in triplicate for a total of 42 samples

2012-07-03 | E-GEOD-39091 | biostudies-arrayexpress

Expression data from polarized macrophages: effect of p53

Project description:p53 is critically important in preventing oncogenesis but its role in non-cancer biology remains unclear. Macrophages exist as two subtypes (M1 and M2). Nutlin-3a (p53 activator) inhibits M2 gene expression and phenotype. p53 acts by suppressing transcription of c-Myc and thence regulates expression of a subset of M2 markers. This work has implications for our understanding of the mechanisms that regulate plasticity of macrophages in health and disease. We used microarrays to study the global programme of gene expression in nutlin-3a and 10058F4 (C-myc inhibitor) treated polarised mouse macrophages 5 groups of cultured mouse macrophages: (i) M0 (untreated), (ii) M1, (iii) M2, (iv) M2+nutlin-3a, (v) M2+MYC inhibitor (10058F4). 3 biological replicates per treatment group.

2015-01-01 | E-GEOD-53321 | biostudies-arrayexpress

Diverse stresses dramatically alter genome-wide p53 binding and transactivation landscape in human cancer cells (Affymetrix)

Project description:The effects of diverse stresses on promoter selectivity and transcription regulation by the tumor suppressor p53 are poorly understood. We have taken a comprehensive approach to characterizing the human p53 network that includes p53 levels, binding, expression and chromatin changes under diverse stresses. Human osteosarcoma U2OS cells treated with anti-cancer drugs Doxorubicin or Nutlin-3 led to strikingly different p53 gene binding patterns based on ChIP-seq experiments. While two contiguous RRRCWWGYYY decamers is the consensus binding motif, p53 can bind a single decamer and function in vivo. Although the number of sites bound by p53 was 6-times greater for Nutlin-3 than Doxorubicin, expression changes induced by Nutlin-3 were much less dramatic compared to Doxorubicin. Unexpectedly, the solvent DMSO alone induced p53 binding to many sites common to Doxorubicin; however, this binding had no effect on target gene expression. Together, these data imply a two-stage mechanism for p53 transactivation where p53 binding only constitutes the first stage. Furthermore, both p53 binding and transactivation were associated with increased active histone modification H3K4me3. We discovered 149 putative new p53 target genes including several that are relevant to tumor suppression, revealing potential new targets for cancer therapy and expanding our understanding of the p53 regulatory network. Gene expression analysis (using Affymetrix Human Genome U133 Plus 2.0 GeneChipÂ® arrays) of the p53 response in U2OS cells treated with either Doxorubicin or Nutlin-3, relative to their controls No Treatment and DMSO, respectively.

2013-07-01 | E-GEOD-46493 | biostudies-arrayexpress

Global analysis of p53-regulated transcription reveals its direct targets and unexpected regulatory mechanisms (GRO-Seq)

Project description:GRO-seq of HCT116 cells treated with Nutlin to activate p53 HCT116 cells were treated with Nutlin or DMSO for 1 hour

2014-05-15 | E-GEOD-53964 | biostudies-arrayexpress

Nutlin-3 treatment of B-CLL

Project description:Background: p53 plays a key role in determining the clinical features of B cell chronic lymphocytic leukemia (CLL). Disruption of p53 by point mutations, deletion at 17p13, or both, occurs in a fraction of cases at diagnosis and predicts poor survival and chemorefractoriness. In cells with functional p53, p53 activity is inhibited through interaction with MDM2. In fact, p53 can be activated upon exposure of cells to inhibitors of p53/MDM2 interaction, like Nutlins. Exposure of CLL cells to Nutlin-3 is effective in raising the levels of p53 protein with subsequent induction of cell cycle arrest and/or apoptosis, independently of the most relevant prognostic markers. Specific gene-sets and GEP were documented to be associated with response or resistance to Nutlin-3 exposure in p53(wt) or p53(del/mut) CLL. These findings may help to identify novel molecular targets for CLL therapy. Aim: to analyze the gene expression profile (GEP) induced by Nutlin-3 exposure in primary CLL cells from p53(wt) and p53(del/mut) cases. Methods: purified cells from 24 PB CLL samples, all characterized for IGHV mutational status, CD38 and ZAP-70 and p53 mutations (16 p53(wt) CLL, 8 p53(del/mut) CLL of which 6 with del17p13 and p53 mutations, 1 with del17p13 alone, and 1 with p53 mutations alone), were exposed to 10 uM Nutlin-3 for 24 hours. GEP was performed using a dual labelling strategy; the differential expression of the below reported genes were validated by quantitative real-time PCR. specific gene-sets and GEP were documented to be associated with response or resistance to Nutlin-3 exposure in p53(wt) or p53(del/mut) CLL. These findings may help to identify novel molecular targets for CLL therapy.

2009-11-11 | GSE18971 | GEO

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