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SRP034601
Homo sapiens
9 Downloadable Samples
IlluminaHiSeq2000
Description
Knockdowns of c-JUN and JUND had opposite effects on PC3 prostate cell migration. We predicted that c-JUN and JUND control the same set of cell migration genes, but in opposite directions. To test this hypothesis, mRNA with expression changes in c-JUN and JUND knockdown PC3 cell lines were compared to mRNA levels in control (luciferase knockdown) PC3 cells by RNA-seq. Overall design: mRNA profiles of luciferase knockdown (WT), c-Jun knockdown, and Jun-D knockdown in PC3 cells were generated using deep sequencing, in triplicate, using Illumina HiSeq. Knockdowns were stable shRNA expression from a lentiviral construct selected with puromycin.
Publication Title
Extracellular signal-regulated kinase signaling regulates the opposing roles of JUN family transcription factors at ETS/AP-1 sites and in cell migration.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
Affymetrix Human Full Length HuGeneFL Array (hu6800), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Up-regulation of expression of the ubiquitin carboxyl-terminal hydrolase L1 gene in human airway epithelium of cigarette smokers.
Sample Metadata Fields
Sex, Age, Race
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Human Full Length HuGeneFL Array (hu6800)
Description
Upregulation of Expression of the Ubiquitin Carboxyl Terminal Hydrolase L1 Gene in Human Airway Epithelium of Cigarette Smokers
Publication Title
Up-regulation of expression of the ubiquitin carboxyl-terminal hydrolase L1 gene in human airway epithelium of cigarette smokers.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 27 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
NOD mice deficient in the transcription factor Batf3 never develop diabetes. The goal of this study was to determine if NOD.Batf3-/- mice islets had any inflammatory signature associated with type 1 diabetes. Islets of Langerhans were isolated from NOD, NOD.Batf3-/-, and NOD.Rag1-/- and then compared to determine inflammatory gene profiles. At 6 and 8 weeks of age, NOD.Batf3-/- islets had an absence of inflammatory gene expression and were almost identical to uninflamed NOD.Rag1-/- islets. This work shows that absence of the Batf3 transcription factor is sufficient to prevent all the inflammatory sequelae of autoimmune diabetes.
Publication Title
A minor subset of Batf3-dependent antigen-presenting cells in islets of Langerhans is essential for the development of autoimmune diabetes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Full Length HuGeneFL Array (hu6800), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Modification of Gene Expression of the Small Airway Epithelium in Response to Cigarette Smoking
Publication Title
Modification of gene expression of the small airway epithelium in response to cigarette smoking.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 118 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Human Full Length HuGeneFL Array (hu6800)
Description
Gamma-aminobutyric acid (GABA) is a multifunctional mediator that functions as a neurotransmitter in the central nervous system and a trophic factor during nervous system development, affecting proliferation, differentiation and cell death [1-3].GABA is synthesized from glutamate, catalyzed by GAD65 and GAD67, glutamic acid decarboxylase {Tillakaratne, Medina-Kauwe, et al. 1995 21 /id}{Owens & Kriegstein 2002 3 /id}{Watanabe, Maemura, et al. 2002 73 /id}. In the CNS transporters and catabolic enzymes work in a coordinated fashion to control the availability of GABA {Tillakaratne, Medina-Kauwe, et al. 1995 21 /id}{Owens & Kriegstein 2002 3 /id}{Watanabe, Maemura, et al. 2002 73 /id} It is now recognized that GABA also functions in a variety of organs outside of the CNS [1,3,4]. In the lung, a series of recent studies suggest that the GABAergic signaling system plays a role in the control of asthma related-airway constriction and mucin secretion [5-9]. In the context that goblet cell hyperplasia and mucin overproduction is associated with cigarette smoking [10-12], we hypothesized that components of the GABAergic system may also be altered in the airway epithelium of cigarette smokers. To assess this hypothesis, we evaluated the expression of the entire GABAergic system in the large and small airway epithelium of healthy nonsmokers and healthy smokers. The data demonstrates there is expression of genes for a complete GABAergic system in the airway epithelium. Interestingly, the expression of GAD67 was markedly modified by smoking, with increased expression in healthy smokers compared to healthy nonsmokers at the mRNA and protein levels. In the context that mucus overproduction is commonly associated with cigarette smoking, GAD67 may be a pharmacologic target for treatment of smoking-related disorders.
Publication Title
Smoking-mediated up-regulation of GAD67 expression in the human airway epithelium.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 33 Downloadable Samples
- Illumina HiSeq 2500
Description
We examined the transcriptional profiles of macrophages that reside in the islets of Langerhans of NOD, NOD.Rag1-/-, and B6.g7 mice at three weeks of age. Islet macrophages expressed an activation signature with high expression of Tnf, Il1b, and MHC-II both at the transcript and protein levels. These features are common with barrier macrophages of the lung and gastrointestinal tract. Moreover, injection of lipopolysaccharide induced a rapid inflammatory gene expression, indicating that blood stimulants are accessible to the macrophages and that these macrophages can sense them. In NOD mice, the autoimmune process imparted an increased inflammatory signature, including elevated expression of chemokines, chemokine receptors, and an oxidative response. The elevated inflammatory signature indicates that the autoimmune program was active at the time of weaning. Thus, the macrophages of the islets of Langerhans are poised to mount an immune response even at steady state, while the presence of the adaptive immune system elevates their activation state. Overall design: We examined the transcriptional profiles of macrophages that reside in the islets of Langerhans of NOD, NOD.Rag1-/-, and B6.g7 mice at three weeks of age. Lung macrophages and pancreatic LN dendritic cells of NOD mice were also examined.
Publication Title
The islet-resident macrophage is in an inflammatory state and senses microbial products in blood.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 68 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Human Full Length HuGeneFL Array (hu6800)
Description
Nuclear factor erythroid 2-related factor 2 (NFE2L2, Nrf2) is an oxidant responsive transcription factor known to induce phase 2 detoxifying and antioxidant genes to protect cells from oxidative stress. Cigarette smoke, with its large oxidant content, is a major stressor to the small airway epithelium, the cells of which are vulnerable to oxidant damage and consequent malignant transformation. In this study, we assessed the role of cigarette smoke in activation of Nrf2 in the human small airway epithelium in vivo. Fiberoptic bronchoscopy was used to sample a pure population of small airway epithelium in 38 healthy nonsmokers and 45 healthy smokers, and gene expression was assessed using Affymetrix HG-U133 Plus 2.0 microarrays. Compared to that of healthy nonsmokers, Nrf2 protein was significantly activated in the small airway epithelium of healthy normal smokers and localized in the nucleus (p<0.05). Of the human homologs of 201 known murine Nrf2-mediated genes, 13 highly smoking-responsive genes were identified (p<10-4, all comparisons smokers to nonsmokers). Using a Nrf2-index to quantify the extent of expression in the small airway epithelium of these 13 known Nrf2 genes, variability in the level of expression was observed among the 45 healthy smokers, but the variability was coordinately modulated among the 13 genes, an observation confirmed by TaqMan quantitative PCR. This variability in the coordinate level of expression of the 13 Nrf2-mediated genes was independent of the smoking history. Based on these observations, the Nrf2 index was used to evaluate whether other genes modulated by smoking in the small airway epithelium were also coordinately up- or down- modulated among the 45 healthy smokers. Two genes, pirin (PIR) and UDP glucuronosyltransferase 1 family polypeptide A4 (UGT1A4), not previously known to be modulated by Nrf2 were identified as being coordinately modulated among the 45 smokers. Both genes contain several functional antioxidant response elements in the promoter region. Using an electrophoretic mobility shift assay, these antioxidant response elements in the promoters of PIR and UGT1A4 responded in vitro to activated Nrf2. These observations are consistent with the concept that Nrf2 plays an important role in regulating cellular defenses against smoking in the highly vulnerable small airway epithelium cell population, and that there is variability among the population in the relative Nrf2 responsiveness to a similar oxidant burden.
Publication Title
Coordinate control of expression of Nrf2-modulated genes in the human small airway epithelium is highly responsive to cigarette smoking.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 55 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Purpose: Despite advances in radical surgery and chemotherapy delivery, ovarian cancer is the most lethal gynecologic malignancy. Most of these patients are treated with platinum-based chemotherapies, but there is no biomarker model to guide their responses to these therapeutic agents. We have developed and independently tested our novel multivariate molecular predictors for forecasting patients' responses to individual drugs on a cohort of 58 ovarian cancer patients.
Publication Title
Multi-gene expression predictors of single drug responses to adjuvant chemotherapy in ovarian carcinoma: predicting platinum resistance.
Sample Metadata Fields
Age, Specimen part, Disease stage, Race
View Samples- Homo sapiens
- 122 Downloadable Samples
- Affymetrix Human Full Length HuGeneFL Array (hu6800), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The aldokatoreductases (AKRs) represent a gene superfamily that code for monomeric, soluble NAD(P)H-dependent oxidoreductases that mediate elimination reactions. AKR1B10, an AKR that functions to eliminate retinals, has been observed to be upregulated in squamous metaplasma and non small cell lung cancer, and has been suggested as a diagnostic marker specific to tobacco-related carcinogenesis. In the context of the link of smoking and lung cancer and the enhanced expression of AKR1B10 expression in lung cancer, we hypothesize that enhanced expression of AKR1B10 may be initiated in healthy smokers, prior to the development of any evidence of lung cancer. For this purpose, expression of AKR1B10 was assessed at the mRNA level using microarrays in the large airway epithelium (21 healthy nonsmokers, 31 health smokers) and small airway epithelium (51 healthy nonsmokers, 58 healthy smokers) obtained by fiberoptic bronchoscopy and brushing, as well as assessment in a subset of this population by TaqMan PCR and in endobronchial biopsies by Western analysis and immunohistochemistry. Compared to healthy nonsmokers, ARK1B10 mRNA levels were markedly upregulated in both the large and small airway epithelium of healthy smokers (large airway microarray p<0.0001, small airway p<0.0001; TaqMan large airway, p<0.02, small airway p<0.01). Consistent with the mRNA data, AKR1B10 protein was significantly upregulated in the airway epithelium of healthy smokers as assessed by Western analysis and by immunohistochemistry, with AKR1B10 expressed in both differentiated and basal cells of the normal epithelium. Finally, cigarette smoke extract mediated up-regulation of AKR1B10 in airway epithelial cells in vitro. Thus, smoking per se mediates up-regulation of AKR1B10 expression in the airway epithelium of healthy smokers with no evidence of lung cancer. In the context of these observations, and the link of AKR1B10 to the metabolism of retinals and to lung cancer, the smoking-induced up-regulation of AKR1B10 may be an early process in the multiple events leading to the develop of lung cancer.
Publication Title
Smoking-induced upregulation of AKR1B10 expression in the airway epithelium of healthy individuals.
Sample Metadata Fields
Sex, Age
View Samples