Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

12 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A Systematic Substrate Screen Links Cyclin D-Dependent Kinases to Senescence Suppression in Cancer Cells through FOXM1

ABSTRACT: Gene expression (mRNA profiling) of U2OS osteosarcoma cells treated with 1 mM of the CDK4/6-specific inhibitor, PD0332991, versus vehicle (DMSO) for 4 hours Here, we monitored the early transcriptional response to acute inhibition of CDK4/6 catalytic activity. As PD0332991 substantially induced senescence in U2OS cells, we performed gene expression arrays from U2OS cells treated with or without PD0332991 for 4 hours. Although this did not result in significant changes in the cell cycle profile, it led to significant changes in global gene expression. 10 total samples were analyzed, i.e. we compared five PD0332991-treated versus five vehicle-treated U2OS cell samples (gene level).

ORGANISM(S): Homo sapiens

SUBMITTER: Lars Anders

PROVIDER: E-GEOD-32182 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Publications

A systematic screen for CDK4/6 substrates links FOXM1 phosphorylation to senescence suppression in cancer cells.

Anders Lars L Ke Nan N Hydbring Per P Choi Yoon J YJ Widlund Hans R HR Chick Joel M JM Zhai Huili H Vidal Marc M Gygi Stephen P SP Braun Pascal P Sicinski Piotr P

Cancer cell 20111101 5

Cyclin D-dependent kinases (CDK4 and CDK6) are positive regulators of cell cycle entry and they are overactive in the majority of human cancers. However, it is currently not completely understood by which cellular mechanisms CDK4/6 promote tumorigenesis, largely due to the limited number of identified substrates. Here we performed a systematic screen for substrates of cyclin D1-CDK4 and cyclin D3-CDK6. We identified the Forkhead Box M1 (FOXM1) transcription factor as a common critical phosphoryl ...[more]

PMID: 22094256

Similar Datasets

Differential gene expression by NKX2-1 suppression in NCI-H2009 cells

Project description:The NKX2-1 transcription factor, a regulator of normal lung development, is the most significantly amplified gene in human lung adenocarcinoma. To better understand how genomic alterations of NKX2-1 drive tumorigenesis, we generated an expression signature associated with NKX2-1 amplification in human lung adenocarcinoma, and analyzed DNA binding sites of NKX2-1 by genome-wide chromatin immunoprecipitation from NKX2-1-amplified human lung adenocarcinoma cell lines. Combining these expression and cistromic analyses identified LMO3, itself encoding a transcription regulator, as a candidate direct transcriptional target of NKX2-1, in addition to consensus binding motifs including a nuclear hormone receptor signature and a Forkhead box motif in NKX2-1-bound sequences. RNA interference analysis of NKX2-1-amplified cells compared to non-amplified cells demonstrated that LMO3 mediates cell proliferation downstream of NKX2-1; cistromic analysis that NKX2-1 may cooperate with FOXA1. Our findings provide new insight into the transcriptional regulatory network of NKX2-1 and suggest that LMO3 is a transducer of lineage specific cell survival of NKX2-1-amplified lung adenocarcinomas. NCI-H2009 cells with stable expression of either pLKO-Tet-Op-shGFP (n=4) or pLKO-Tet-Op-shNKX2-1 (pooled population; n=3 and a clone; n=3) were treated with 50ng/ml of doxycyline for 48 hours. Total RNA was extracted, gene expression profiling was performed and differential gene expression between shGFP and shNKX2-1 was analyzed to determine the effects by suppression of NKX2-1 in NCI-H2009 cells.

2013-04-15 | E-GEOD-40270 | biostudies-arrayexpress

NLRC5 is a transcriptional regulator of MHC class I genes

Project description:NLRC5 is a member of the NLR family of proteins. The observation that NLRC5 is found in the nucleus prompted us to perform a gene array to identify putative target genes of NLRC5. We generated Jurkat T cell lines that stably express either the wild-type or mutant forms of NLRC5 harboring mutations in the nucleotide binding domain (NBD): Walker A (deficient in nucleotide binding), Walker B (deficient in nucleotide hydrolysis), and the combined Walker AB, carrying both mutations. Site-directed mutagenesis was used to create the NLRC5 NBD mutants: Walker A (K234A), Walker B (E311Q), and Walker AB (both mutations). We compared the expression profiles of Jurkat T cells expressing GFP, or the GFP-tagged wild-type, Walker A, Walker B, or Walker AB forms of NLRC5. GFP and the Walker A and Walker AB forms of NLRC5 were considered functionally inactive, while the wild-type and Walker B forms of NLRC5 were considered functionally active. These groups were used as biological replicates to assess the effect of NLRC5 activity on gene expression.

2010-07-30 | E-GEOD-22064 | biostudies-arrayexpress

Blockade of the neogenin-RGMb-BMP signaling hub inhibits allergen-induced airway hyperreactivtiy

Project description:Bronchial asthma is associated with type 2 immune responses induced by components of adaptive as well as innate immunity. Although innate cytokines such as IL-25 have been shown to play key roles in development of airway hyperreactivity (AHR), little is known of innate molecules that regulate IL-25-mediated airway inflammation. We found that blockade of repulsive guidance molecule b (RGMb) in an experimental murine model of asthma blocked the development of AHR, a cardinal feature of asthma, and that RGMb is expressed on F4/80+CD11b+CD11cneg macrophages (RGMb+ macrophages), which accumulated in the lungs of OVA-sensitized and challenged mice, but not in naÃ¯ve mice. Moreover, we found that a large fraction of the RGMb+ macrophages expressed the IL-25 receptor IL-17RB and produced IL-13. IL-25 was critical for the development of AHR in our model, since mice deficient in IL-17RB did not develop AHR. Finally, treatment with anti-RGMb mAb during the challenge phase of the protocol after allergen sensitization effectively prevented the development of AHR and airway inflammation, suggesting for the first time that RGMb+ cells, including RGMb+ macrophages, play critical roles in allergen-induced asthma. We used microarrays to compare the gene expression patterns in WT mice sensitized and challenged with OVA that were treated with either RGMb mAb or an isotype control. First replicate: 3 control samples (mice sensitized and challenged with saline), 3 RGMb mAb samples, 3 isotype samples; 2nd replicate: 3 control samples, 3 RGMb mAb samples, 2 isotype samples. Lung tissues were harvested at the same treatment time point in all groups.

2016-03-14 | E-GEOD-79156 | biostudies-arrayexpress

Functional analysis of ABCB5 in melanoma cells

Project description:Functional analysis of ABCB5 in A375 and G3361 melanoma cells, by comparing stably-transfected controls to ABCB5-shRNA-targeted cells. 12 samples total. Replicates n=3 for the following 4 groups: A375 pSUPER-retro-puro-Vector vs. A375 pSUPER-retro-puro-ABCB5-KD; G3361 pSUPER-retro-puro-shCNTRL vs. G3361 pSUPER-retro-puro-ABCB5-KD.

2014-06-17 | E-GEOD-38290 | biostudies-arrayexpress

Eed conditional knockout in chondrocytes

Project description:Primary rib chondrocyte were isoloated from P0.5-day old wildtype and Col2-Cre:floxed EED conditional knockout mouse pups,and cultured overnight in 10%FCS containing DMEM. RNA was isolated and subjected to Affymetrix Mouse Gene ST 1.0 array. Primary rib chondrocyte were isoloated from P0.5-day old wildtype and Col2-Cre:floxed EED conditional knockout mouse pups,and cultured overnight in 10%FCS containing DMEM. RNA was isolated and subjected to Affymetrix Mouse Gene ST 1.0 array. Biological duplicate. Mice were in a mixed genetic background of C57/B6 and 129sv.

2015-11-01 | E-GEOD-66862 | biostudies-arrayexpress

An Integrated Approach to Uncover Drivers of Cancer

Project description:We developed a computational framework that integrates chromosomal copy number and gene expression data for detecting aberrations that promote cancer progression. We demonstrate the utility of this framework using a melanoma dataset. Our analysis correctly identified known drivers of melanoma and predicted multiple novel tumor dependencies. Two dependencies, TBC1D16 and RAB27A, confirmed empirically, suggest that abnormal regulation of protein trafficking contributes to proliferation in melanoma. Together, these results demonstrate the ability of integrative Bayesian approaches to identify novel candidate drivers with biological, and possibly therapeutic, importance in cancer. Effects of knockdown of two genes -TBC1D16 and RAB27A - were tested on four cell lines each, each of them with two different hairpins. As a control, we used a hairping targeting GFP. shGFP experiments were done in biological duplicates or more. The second WM1976-shGFP sample was identified as an outlier by a PCA analysis and was excluded from our analysis.

2010-12-01 | E-GEOD-23884 | biostudies-arrayexpress

Affymetrix SNP array data for human prostate tumor samples

Project description:Metabolomics was used to identify metabolic fingerprints of AKT1 activation or MYC overexpression in human prostate tumors. Genomics was used to determine how many of these tumors had a genetic aberration underlying signaling activation. Copy number analysis of Affymetrix 250K SNP arrays was performed for 59 human prostate tumors and 6 normal prostate samples.

2014-10-20 | E-GEOD-62218 | biostudies-arrayexpress

Transcription profiling of mouse CD71+/Ter-119+ bone marrow erythroid progenitors from Rb-null animals and controls reveals Rb intrinsically promotes erythropoiesis by coupling cell cycle exit with mitochondrial biogenesis

Project description:Regulation of the cell cycle is intimately linked to erythroid differentiation, yet how these processes are coupled is not well understood. To gain insight into this coordinate regulation, we examined the role that the retinoblastoma protein (Rb), a central regulator of the cell cycle, plays in erythropoiesis. We found that Rb serves a cell-intrinsic role and its absence causes ineffective erythropoiesis, with a differentiation block at the transition from early to late erythroblasts. Unexpectedly, in addition to a failure to properly exit the cell cycle, mitochondrial biogenesis fails to be upregulated concomitantly, contributing to this differentiation block. The link between erythropoiesis and mitochondrial function was validated by inhibition of mitochondrial biogenesis. Erythropoiesis in the absence of Rb resembles the human myelodysplastic syndromes, where defects in cell cycle regulation and mitochondrial function frequently occur. Our work demonstrates how these seemingly disparate pathways play a role in coordinately regulating cellular differentiation. Experiment Overall Design: Microarray expression analysis from sorted CD71+/Ter-119+ bone marrow erythroid progenitors of Rb-null animals and controls. The Rb-null genotype was EpoR-GFPcre/+; Rb fl/fl and the control genotype was EpoR-GFPcre/+; Rb fl/+. We have analyzed 3 Rb-null datasets and 3 control datasets.

2008-04-07 | E-GEOD-9717 | biostudies-arrayexpress

Reactivation of ERK signaling causes resistance to EGFR kinase inhibitors

Project description:This SuperSeries is composed of the following subset Series: GSE37698: Reactivation of ERK signaling causes resistance to EGFR kinase inhibitors (SNP array) GSE37699: Aberrant ERK signaling causes resistance to EGFR kinase inhibitors Refer to individual Series

2012-10-01 | E-GEOD-37700 | biostudies-arrayexpress

Reactivation of ERK signaling causes resistance to EGFR kinase inhibitors (SNP array)

Project description:The clinical efficacy of EGFR kinase inhibitors is limited by the development of drug resistance. The irreversible EGFR kinase inhibitor WZ4002 is effective against the most common mechanism of drug resistance mediated by the EGFR T790M mutation. Here we show that in multiple complementary models harboring EGFR T790M, resistance to WZ4002 develops through aberrant activation of ERK signaling caused by either an amplification of MAPK1 or by downregulation of negative regulators of ERK signaling. Inhibition of MEK or ERK restores sensitivity to WZ4002, and the combination of WZ4002 and a MEK inhibitor prevents the emergence of drug resistance. The WZ4002 resistant MAPK1 amplified cells also demonstrate an increase both in EGFR internalization and a decrease in sensitivity to cytotoxic chemotherapy compared to the parental counterparts. Our findings provide insights into mechanisms of drug resistance to EGFR kinase inhibitors and highlight rational combination therapies that should be evaluated in clinical trials. The EGFR mutant non-small cell lung cancer (NSCLC) cell line PC9 GR4 (delE746_A750/T790M) was exposed to increasing concentrations of WZ4002 similar to previously described methods. Individual clones from WZ4002-resistant (WZR) cells were isolated and confirmed to be drug resistant. Number of samples: 5. PC9GR4 as a control. 4 clones of WZ4002-resistant PC9GR4.

2012-10-01 | E-GEOD-37698 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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