Filters
Technology
Platform
GSE16424
Homo sapiens
18 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Advanced ovarian cancers are initially responsive to chemotherapy with platinum drugs but develop drug resistance in most cases. We showed recently that hepatocyte growth factor (HGF) enhances death of human ovarian cancer cell lines treated with cisplatin (CDDP) and that this effect is mediated by the p38 mitogen-activated protein kinase. In this work, we integrated genome-wide expression profiling, in silico data survey, and functional assays to identify transcripts regulated in SK-OV-3 ovarian cancer cells made more responsive to CDDP by HGF. Using oligonucleotide microarrays, we found that HGF pretreatment changes the transcriptional response to CDDP. Quantitative reverse transcription-PCR not only validated all the 15 most differentially expressed genes but also confirmed that they were primarily modulated by the combined treatment with HGF and CDDP and reversed by suppressing p38 mitogen-activated protein kinase activity. Among the differentially expressed genes, we focused functional analysis on two regulatory subunits of the protein phosphatase 2A, which were down-modulated by HGF plus CDDP. Decrease of each subunit by RNA interference made ovarian cancer cells more responsive to CDDP, mimicking the effect of HGF. In conclusion, we show that HGF and CDDP modulate transcription in ovarian cancer cells and that this transcriptional response is involved in apoptosis regulation. We also provide the proof-of-concept that the identified genes might be targeted to either increase the efficacy of chemotherapeutics or revert chemotherapy resistance.
Publication Title
Genes regulated by hepatocyte growth factor as targets to sensitize ovarian cancer cells to cisplatin.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Metabolism in cancer serves to provide energy and key biomolecules that sustain cell growth, a process that is frequently accompanied by decreased mitochondrial use of glucose. Importantly, metabolic intermediates including mitochondrial metabolites are central substrates for post-translational modifications at the core of cellular signalling and epigenetics. However, the molecular means that coordinate the use of mitochondrial metabolites for anabolism and nuclear protein modification are poorly understood. Here, we unexpectedly found that genetic and pharmacological inactivation of Pyruvate Dehydrogenase A1 (PDHA1), a subunit of pyruvate dehydrogenase complex (PDC) that regulates mitochondrial metabolism16 inhibits prostate cancer development in different mouse and human xenograft tumour models. Intriguingly, we found that lipid biosynthesis was strongly affected in prostate tumours upon PDC inactivation. Mechanistically, we found that nuclear PDC controls the expression of Sterol regulatory element-binding transcription factor (SREBF) target genes by mediating histone acetylation whereas mitochondrial PDC provides cytosolic citrate for lipid synthesis in a coordinated effort to sustain anabolism. In line with the oncogenic function of PDC in prostate cancer, we find that PDHA1 and the PDC activator, Pyruvate dehydrogenase phospatase 1 (PDP1), are frequently amplified and overexpressed at both gene and protein level in these tumours. Taken together, our findings demonstrate that both mitochondrial and nuclear PDC sustains prostate tumourigenesis by controlling lipid biosynthesis thereby pointing at this complex as a novel target for cancer therapy.
Publication Title
Compartmentalized activities of the pyruvate dehydrogenase complex sustain lipogenesis in prostate cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 46 Downloadable Samples
- Sentrix Human-6 Expression BeadChip
Description
Special AT-rich binding protein 1 (SATB1) is a global chromatin organizer and a transcription factor induced by interleukin-4 (IL-4) during the early T helper 2 (Th2) cell differentiation. In this study, we investigated the role of SATB1 in T helper cell differentiation by performing gene expression profiling of human differentiating Th cells in which expression of SATB1 was downregulated by RNA interference (RNAi). Our results indicate that SATB1 is involved in the regulation of more than three hundred genes in primary human CD4+ T cells, including several IL-12 and/or IL-4 regulated factors, suggesting a role in the development or function of Th subtypes.
Publication Title
SATB1 dictates expression of multiple genes including IL-5 involved in human T helper cell differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 28 Downloadable Samples
Affymetrix Mouse Expression 430A Array (moe430a), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Expression signatures of metastatic capacity in a genetic mouse model of lung adenocarcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The biologic basis for NSCLC metastasis is not well understood. Here we addressed this deficiency by transcriptionally profiling tumors from a genetic mouse model of human lung adenocarcinoma that develops metastatic disease owing to the expression of K-rasG12D and p53R172H. We identified 2,209 genes that were differentially expressed in distant metastases relative to matched lung tumors. Mining of publicly available data bases revealed this expression signature in a subset of NSCLC patients who had a poorer prognosis than those without the signature.
Publication Title
Expression signatures of metastatic capacity in a genetic mouse model of lung adenocarcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The aim of this study was to identify genes regulated by IL-12, IL-18 and IFN-alpha during early differentiation of human Th1 cells
Publication Title
Activating transcription factor 3 is a positive regulator of human IFNG gene expression.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
The aim of the dataset was to study on genome-wide level the effect of PIM kinase (PIM1+PIM2+PIM3) knockdown in gene expression on early differentiation of human cord blood derived CD4+ T cells cultured under Th1 (Act+IL12) polarizing conditions.
Publication Title
Proviral integration site for Moloney murine leukemia virus (PIM) kinases promote human T helper 1 cell differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We found that hyperglycemia and elevated fatty acids in diabetes could activate protein kinase C- isoforms and selectively induce insulin resistance via inhibiting vascular insulin signaling.
Publication Title
Insulin decreases atherosclerosis by inducing endothelin receptor B expression.
Sample Metadata Fields
Age, Specimen part, Disease, Disease stage, Treatment
View Samples- Homo sapiens
- 55 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The requirement of frozen tissues for microarray experiments limits the clinical usage of genome-wide expression profiling using microarray technology.
Publication Title
Robust gene expression signature from formalin-fixed paraffin-embedded samples predicts prognosis of non-small-cell lung cancer patients.
Sample Metadata Fields
Sex, Specimen part, Race
View Samples- Homo sapiens
- 111 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Illumina human-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide profiling of interleukin-4 and STAT6 transcription factor regulation of human Th2 cell programming.
Sample Metadata Fields
Specimen part
View Samples