Filters
Technology
Platform
GSE58386
Homo sapiens
8 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
In pancreatic cancer the survival rate is low, as the available treatment options usually only extend survival and seldom produce a cure. Drug resistance and disease reoccurrence is the typical reason for death after cancer diagnosis. 5-Fluorouracil (5-FU) is the main chemostatic used in first line therapy. However the majority of the tumors become resistant to treatment. To investigate acquired 5-FU resistance in pancreatic adenocarcinoma, we established chemoresistant monoclonal cell lines from the Panc03.27 cell line by long-term exposure to 5-FU. In addition to increased expression of markers associated with multidrug resistance, the 5-FU resistant clones showed alterations typical of the process of epithelial-to-mesenchymal transition (EMT), including upregulation of mesenchymal markers and increased invasiveness. Microarray analysis revealed the L1CAM pathway as one of the most upregulated pathways in the chemoresistant clones, which was confirmed on RNA and protein levels. Expression of the adhesion molecule L1CAM is associated with a chemoresistant and migratory phenotype of pancreatic cancer. Using esiRNA targeting L1CAM, or by blocking the extracellular part of L1CAM with monoclonal antibodies, we discovered that the increased invasiveness observed in the chemoresistant cells depends on L1CAM. Using esiRNA targeting -catenin and/or Slug, we discovered that L1CAM expression depends on Slug rather than -catenin in the 5-FU resistant cells. We demonstrate a functional link between Slug and the expression level of L1CAM in pancreatic cancer cells having undergone EMT following long-term exposure to 5-FU. Our findings provide further insight into the molecular mechanisms leading to a chemoresistant and migratory phenotype in pancreatic cancer cells and indicate the importance of Slug-induced L1CAM in refractory pancreatic cancer.
Publication Title
Slug-dependent upregulation of L1CAM is responsible for the increased invasion potential of pancreatic cancer cells following long-term 5-FU treatment.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Dysregulation of MITF Leads to Transformation in MC1R-Defective Melanocytes.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Expression analysis of immortalized melanocytes Hermes 3c and Hermes 4c derivative cell lines following lentiviral transduction of a HA-tagged MITF-M construct (pLX3xHAvar4mCherry) or control construct (pLVX IRES mCherry).
Publication Title
Dysregulation of MITF Leads to Transformation in MC1R-Defective Melanocytes.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
c-Myc Antagonises the Transcriptional Activity of the Androgen Receptor in Prostate Cancer Affecting Key Gene Networks.
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Prostate cancer is the most common non-cutaneous cancer in men. The androgen receptor (AR) a ligand-activated transcription factor, constitutes the main drug target for advanced cases of the disease. However, a variety of other transcription factors and signalling networks have been shown to be altered in patients and to influence AR activity. The oncogenic transcription factor c-Myc has been studied extensively in multiple malignancies, but its impact on AR activity in prostate cancer remains elusive. In this study we assessed the impact of clinically relevant levels of c-Myc overexpression on AR activity and transcriptional output. We found that c-Myc and the AR share a substantial amount of binding sites, which exhibit enhancer-like characteristics. Interestingly, c-Myc overexpression altered global AR chromatin occupancy and antagonised a subset of androgen-induced genes. Furthermore, c-Myc overexpression modified histone marks, most notably H3K4me1 and H3K27me3. Lastly, we validated the antagonistic relationship between c-Myc and two AR target genes, KLK3 and GNMT, in patient samples.
Publication Title
c-Myc Antagonises the Transcriptional Activity of the Androgen Receptor in Prostate Cancer Affecting Key Gene Networks.
Sample Metadata Fields
Time
View Samples- Macaca mulatta
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Circadian regulation of gene expression in central and peripheral tissue has been studied in mice. The biomedical implications of this findings led us to the development of a model in which to study the circadian mechanisms underlying primate physiology.
Publication Title
Twenty-four-hour rhythmic gene expression in the rhesus macaque adrenal gland.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cell cycle-coupled expansion of AR activity promotes cancer progression.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Evaluation of the genome wide impact of cell cycle position on DHT stimulated gene expression programs. Results show differential cell cycle regulated gene expression in different cell cycle phases.
Publication Title
Cell cycle-coupled expansion of AR activity promotes cancer progression.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
IlluminaHiSeq2000
Description
Prostate cancer is the most common male cancer and androgen receptor (AR) is the major driver of the disease. Here we show that Enoyl-CoA delta isomerase 2 (ECI2) is a novel AR-target that promotes prostate cancer cell survival. Increased ECI2 expression predicts mortality in prostate cancer patients (p=0.0086). ECI2 encodes for an enzyme involved in lipid metabolism, and we use multiple metabolite profiling platforms and RNA-seq to show that inhibition of ECI2 expression leads to decreased glucose utilization, accumulation of fatty acids and down-regulation of cell cycle related genes. In normal cells, decrease in fatty acid degradation is compensated by increased consumption of glucose, and here we demonstrate that prostate cancer cells are not able to respond to decreased fatty acid degradation. Instead, prostate cancer cells activate incomplete autophagy, which is followed by activation of the cell death response. Finally, we identified a clinically approved compound, perhexiline, which inhibits fatty acid degradation, and replicates the major findings for ECI2 knockdown. This work shows that prostate cancer cells require lipid degradation for survival and identifies a small molecule inhibitor with therapeutic potential. Overall design: Two biological replicates for prostate cancer cell line (LNCaP) and cell line representing normal prostate epithelium (RWPE-1), transfected with scrambled siRNA or two different siRNAs targeting ECI2. RNA was extracted and used for RNA-sequencing. The processed files provided are compressed folders containing multiple output files from CuffDiff runs estimating differentially expressed transcripts between the indicated ECI2 siRNA treated cells versus cells treated with Scrambled siRNAs.
Publication Title
Lipid degradation promotes prostate cancer cell survival.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 34 Downloadable Samples
- Illumina HiSeq 2000
Description
Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease usually caused by large homozygous expansions of GAA repeat sequences in intron 1 of the frataxin (FXN) gene. FRDA patients have low FXN mRNA and frataxin protein levels when compared with heterozygous carriers or healthy controls. Presently, there is no effective treatment for FRDA, and biomarkers to measure therapeutic trial outcomes and/or to gauge disease progression are lacking. Peripheral tissues, including blood cells, buccal cells, and skin fibroblasts, can readily be isolated from FRDA patients and used to define molecular hallmarks of disease pathogenesis. However, because these tissues are not directly involved in disease pathogenesis, their relevance as models of the molecular aspects of the disease is yet to be decided. Transcriptome profiling of FRDA skin fibroblasts revealed significantly upregulated expression of genes encoding plasma membrane solute carrier proteins. Conversely, the expression of genes encoding accessory factors and enzymes involved in cytoplasmic and mitochondrial protein synthesis was consistently decreased in the FRDA cells. Finally, comparison of genes differentially expressed in FRDA fibroblasts to 3 previously published gene expression signatures defined for FRDA blood cells showed substantial overlap between the independent datasets, including correspondingly deficient expression of antioxidant defense genes. Together, these results indicate that gene expression profiling of cells derived from peripheral tissues can, in fact, consistently reveal novel molecular pathways of the disease. Overall design: We used RNA sequencing to profile the transcriptomes of primary fibroblast cell lines derived from 18 FRDA patients and 17 unaffected control individuals.
Publication Title
A Comprehensive Transcriptome Analysis Identifies FXN and BDNF as Novel Targets of miRNAs in Friedreich's Ataxia Patients.
Sample Metadata Fields
Specimen part, Subject
View Samples