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GSE47777
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
C/EBP is an important regulator of oncogene-induced senescence (OIS). Here we show that C/EBP, a heterodimeric partner of C/EBP whose biological functions are not well understood, inhibits cellular senescence. Cebpg-/- MEFs proliferated poorly, entered senescence prematurely, and expressed a pro-inflammatory gene signature, including elevated levels of senescence-associated secretory phenotype (SASP) genes whose induction by oncogenic stress requires C/EBP. The senescence-suppressing activity of C/EBP required its ability to heterodimerize with C/EBP. Covalently linked C/EBP homodimers (~) inhibited the proliferation and tumorigenicity of RasV12-transformed NIH3T3 cells, activated SASP gene expression, and recruited the CBP co-activator in a Ras-dependent manner, whereas ~ heterodimers lacked these capabilities and efficiently rescued proliferation of Cebpg-/- MEFs. C/EBP depletion partially restored growth of C/EBP-deficient cells, indicating that the increased levels of C/EBP homodimers in Cebpg-/- MEFs inhibit proliferation. The proliferative functions of C/EBP are not restricted to fibroblasts, as hematopoietic progenitors from Cebpg-/- bone marrow also displayed impaired growth. Furthermore, high CEBPG expression correlated with poorer clinical prognoses in several human cancers, and C/EBP depletion decreased proliferation and induced senescence in lung tumor cells. Our findings demonstrate that C/EBP neutralizes the cytostatic activity of C/EBP through heterodimerization, which prevents senescence and suppresses basal transcription of SASP genes.
Publication Title
C/EBPγ suppresses senescence and inflammatory gene expression by heterodimerizing with C/EBPβ.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
LPS independent activation of the pro-inflammatory receptor Trem1 by C/EBPε in granulocytes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
To identify target genes of C/EBPepsilon in differentiated granulocytes, total RNA were purified from sorted Gr-1intermediate/Mac-1+ and Gr-1hi/Mac-1+ cells of C/EBPepsilon knock out and C57BL/6 wild type mice using RNeasy Mini Kit (Qiagen). The differences of their expression pattern were compared with Illumina Mouse WG-6v2 Expression Chip platform. Raw Illumina BeadArray data in IDAT format were preprocessed using the open-source Bioconductor package illuminaio with the Illumina array design formation BGX file downloaded from NCBI, GEO accession: GPL6887. Following the preprocessing, the expression data were normalized by applying control background correction, log transformation and inter-quantile normalization using the neqc function from the limma bioconductor package. This allowed us to compare the transcriptomic consequences of C/EBPepsilon in two independent populations.
Publication Title
LPS independent activation of the pro-inflammatory receptor Trem1 by C/EBPε in granulocytes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 60 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Background: Information on the carcinogenic potential of chemicals is only availably for High Production Volume products. There is however, a pressing need for alternative methods allowing for the chronic toxicity of substances, including carcinogenicity, to be detected earlier and more reliably. Here we applied advanced genomics to a cellular transformation assay to identify gene signatures useful for the prediction of risk for carcinogenicity. Methods: Genome wide gene expression analysis and qRT-PCR were applied to untransformed and transformed Balb/c 3T3 cells that exposed to 2, 4-diaminotoluene (DAT), benzo(a)pyrene (BaP), 2-Acetylaminoflourene (AAF) and 3-methycholanthrene (MCA) for 24h and 120h, at different concentrations, respectively. Furthermore, various bioinformatics tools were used to identify gene signatures predicting for the carcinogenic risk. Results: Bioinformatics analysis revealed distinct datasets for the individual chemicals tested while the number of significantly regulated genes increased with ascending treatment concentration of the cell cultures. Filtering of the data revealed a common gene signature that comprised of 13 genes whose regulation in cancer tissue has already been established. Strikingly, this gene signature was already identified prior to cell transformation therefore confirming the predictive power of this gene signature in identifying carcinogenic risks of chemicals. Comparison of fold changes determined by microarray analysis and qRT-PCR were in good agreement. Conclusion: Our data describes selective and commonly regulated carcinogenic pathways observed in an easy to use in vitro carcinogenicity assay. Here we defined a set of genes which can serve as a simply assay to predict the risk for carcinogenicity by use of an alternative in vitro testing strategy.
Publication Title
Toxicogenomics applied to in vitro carcinogenicity testing with Balb/c 3T3 cells revealed a gene signature predictive of chemical carcinogens.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Up to now the role of tumor-specific pTregs and anergic cells during tumor development is not fully understood. Here we used a genetically-induced tumor expressing a MHC-II restricted DBY model antigen to characterize the tumor-induced pTregs and anergic cells that arise early during tumor development.
Publication Title
Induction of anergic or regulatory tumor-specific CD4<sup>+</sup> T cells in the tumor-draining lymph node.
Sample Metadata Fields
Time
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Up to know CD4 T cell antitumor responses have been mostly studied in transplanted tumor models. However, although they are valuable tools, they are not suitable to study the long term interactions between tumors and the immune system
Publication Title
Induction of anergic or regulatory tumor-specific CD4<sup>+</sup> T cells in the tumor-draining lymph node.
Sample Metadata Fields
Time
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
CD4+ T cells as mediators of antitumor responses are beginning to be appreciated. Our team demonstrated that chronically activated CD4+ T cells (chCD4+ T cells) were expanded in the blood of cancer patients and their expansion is correlated with tumor regression.
Publication Title
Induction of anergic or regulatory tumor-specific CD4<sup>+</sup> T cells in the tumor-draining lymph node.
Sample Metadata Fields
Disease
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The level of trypsin-2 has been shown to correlate with the malignancy and metastatic potential of many cancer.
Publication Title
Trypsin-2 enhances carcinoma invasion by processing tight junctions and activating ProMT1-MMP.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Danio rerio
- 6 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
The production of functional mRNA involves multiple steps including transcription initiation, elongation, and termination. spt5 encodes a conserved essential transcription elongation factor that controls RNAPII processivity in vitro and co-localizes with RNAPII in vivo.
Publication Title
Identification of Spt5 target genes in zebrafish development reveals its dual activity in vivo.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Transforming growth factor beta 1 (TGF-1) is the most extensively studied growth factor in dentin-pulp complex, with pleiotropic effects on pulp response and healing. Our main objective was to analyze the expression profile of pulp tissue and odontoblasts, and the effects of TGF-1 on these profiles in cultured human pulp and odontoblasts with a specific interest in the anti- and pro-inflammatory cytokines.
Publication Title
Effects of TGF-beta 1 on interleukin profile of human dental pulp and odontoblasts.
Sample Metadata Fields
No sample metadata fields
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