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GSE6043
Homo sapiens
7 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Deregulation of translational control is an obligatory step in oncogenesis; however, this step has not been addressed by prior genomic and transcriptional profiling studies of cancer biology. Here we simulate the translational deregulation found in cancer by ectopically over expressing translation initiation factor eIF4E in primary human mammary epithelial cells; and examine its impact on cell biology and the pattern of ribosomal recruitment to mRNA genome wide. Over expression of eIF4E allows cells to bypass M0 premature growth arrest, but does not confer other malignant properties. However, in concert with hTERT, eIF4E imparts cells with growth and survival autonomy - and profoundly alters the pattern of polyribosome-associated mRNA encoding cell cycle and apoptosis regulators. The translational response to increased eIF4E is not only a unidirectional activation of oncogenic drivers, but also consists of complex intrinsic translational mechanisms that mitigate the acquisition of neoplastic properties.
Publication Title
Eukaryotic translation initiation factor 4E induced progression of primary human mammary epithelial cells along the cancer pathway is associated with targeted translational deregulation of oncogenic drivers and inhibitors.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
Illumina Genome Analyzer II, Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
TET1 is a maintenance DNA demethylase that prevents methylation spreading in differentiated cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 5 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st), Illumina Genome Analyzer II
Description
We report that full length TET1 (TET1-FL) overexpression fails to induce global DNA demethylation in HEK293T cells. The preferential binding of TET1-FL to hypomethylated CpG islands (CGIs) through its CXXC domain leads to its inhibited 5-hydroxymethylcytosine (5hmC) production as methylation level increases. TET1-FL-induced 5hmC accumulates at CGI edges, while TET1 knockdown induces methylation spreading from methylated edges into hypomethylated CGIs. However, TET1 can regulate gene transcription independent of its dioxygenase catalytic function. Thus, our results identify TET1 as a maintenance DNA demethylase that does not purposely decrease methylation levels, but specifically maintains the DNA hypomethylation state of CGIs in adult cells.
Publication Title
TET1 is a maintenance DNA demethylase that prevents methylation spreading in differentiated cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus, Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st), Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Probe Name version)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Therapeutic targeting of the MYC signal by inhibition of histone chaperone FACT in neuroblastoma.
Sample Metadata Fields
Age, Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 2 Downloadable Samples
- Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Probe Name version), Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Amplification of the MYCN oncogene predicts treatment resistance in childhood neuroblastoma. Using a MYC target gene signature that predicts poor neuroblastoma prognosis we identified the histone chaperone, FAcilitates Chromatin Transcription (FACT), as a crucial mediator of the MYC signal and a therapeutic target in the disease. FACT and MYCN expression created a forward feedback loop in neuroblastoma cells that was essential for maintaining mutual high expression. FACT inhibition by the small molecule Curaxin compound, CBL0137, markedly reduced tumor initiation and progression in vivo. CBL0137 exhibited strong synergy with chemotherapy in standard use by blocking repair of DNA damage caused by genotoxic drugs, thus creating a synthetic lethal environment in MYCN amplified neuroblastoma cells and a treatment strategy for MYCN-driven neuroblastoma
Publication Title
Therapeutic targeting of the MYC signal by inhibition of histone chaperone FACT in neuroblastoma.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Amplification of the MYCN oncogene predicts treatment resistance in childhood neuroblastoma. Using a MYC target gene signature that predicts poor neuroblastoma prognosis we identified the histone chaperone, FAcilitates Chromatin Transcription (FACT), as a crucial mediator of the MYC signal and a therapeutic target in the disease. FACT and MYCN expression created a forward feedback loop in neuroblastoma cells that was essential for maintaining mutual high expression. FACT inhibition by the small molecule Curaxin compound, CBL0137, markedly reduced tumor initiation and progression in vivo. CBL0137 exhibited strong synergy with chemotherapy in standard use by blocking repair of DNA damage caused by genotoxic drugs, thus creating a synthetic lethal environment in MYCN amplified neuroblastoma cells and a treatment strategy for MYCN-driven neuroblastoma
Publication Title
Therapeutic targeting of the MYC signal by inhibition of histone chaperone FACT in neuroblastoma.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcriptomic response of mouse mixed neuron-glial cell cultures to 1,25-dihydroxyvitamin D3
Publication Title
The transcriptomic response of mixed neuron-glial cell cultures to 1,25-dihydroxyvitamin d3 includes genes limiting the progression of neurodegenerative diseases.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Rattus norvegicus
- 14 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
We used Affymetrix microarrays to investigate gene expression changes in the liver of lean female Zucker rats exposed to a normal diet supplemented with a rosemary extract rich in the diterpenic compound, carnosic acid (CA).
Publication Title
A rosemary extract enriched in carnosic acid improves circulating adipocytokines and modulates key metabolic sensors in lean Zucker rats: Critical and contrasting differences in the obese genotype.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Homo sapiens
- 58 Downloadable Samples
- IlluminaHiSeq2500
Description
RNA-seq was performed after MCF7 cells were treated with S2101, UNC0638, GSK343, depsipeptide alone or in combination with decitabine Overall design: Biological triplicates were performed for a total of 30 samples. Fold change of each gene was calculated by comparing change in expression after inhibitor treatment to expression in the control samples
Publication Title
Transcriptional Selectivity of Epigenetic Therapy in Cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 60 Downloadable Samples
- IlluminaHiSeq2500
Description
RNA-seq was performed after HL60 cells were treated with S2101, UNC0638, GSK343, depsipeptide alone or in combination with decitabine Overall design: Biological triplicates were performed for a total of 30 samples. Fold change of each gene was calculated by comparing change in expression after inhibitor treatment to expression in the control samples
Publication Title
Transcriptional Selectivity of Epigenetic Therapy in Cancer.
Sample Metadata Fields
No sample metadata fields
View Samples