We performed RNA sequencing in isogenic models of COX-1 proficient (OV3/SCR) and COX-1 deficient (OV3/COX1KD) OVCAR-3 ovarian cancer cells. COX-1 knockdown was associated with a coordinated anti-oncogenic phenotype, with growth, angiogenesis, migration/invasion, and epithelial-mesenchymal transition among the pathways down-regulated. Overall design: RNA sequencing was performed at Vanderbilt Technologies for Advanced Genomics (VANTAGE) using Illumina HiSeq 2500.
Aberrant over-expression of COX-1 intersects multiple pro-tumorigenic pathways in high-grade serous ovarian cancer.
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View SamplesThe origin and function of human double negative (DN) TCR-alpha/beta T cells is unknown. They are thought to contribute to the pathogenesis of systemic lupus erythematosus because they expand and accumulate in inflamed organs. Here we provide evidence that human TCR-alpha/beta CD4- CD8- DN T cells derive exclusively from activated CD8+ T cells. Freshly isolated TCR-alpha/beta DN T cells display a distinct gene expression and cytokine production profile. DN cells isolated from peripheral blood as well as DN cells derived in vitro from CD8+ T cells, produce a defined array of pro-inflammatory mediators that includes IL-1, IL-17, IFN-gama, CXCL3, and CXCL2. These results indicate that, upon activation, CD8+ T cells have the capacity to acquire a distinct phenotype that grants them inflammatory capacity.
Human TCR-alpha beta+ CD4- CD8- T cells can derive from CD8+ T cells and display an inflammatory effector phenotype.
Specimen part
View SamplesHere we show that platinum-resistant ovarian cancer cells also show reduced cholesterol biosynthesis, and mostly rely on uptake of exogenous cholesterol for their needs. Expression of FDPS and OSC, enzymes involved in cholesterol synthesis, are decreased both in drug-resistant cells and upon TRAP1 silencing, whereas the expression of LDL receptor, the main mediator of extracellular cholesterol uptake, is increased. Strikingly, treatment with different statins to inhibit cholesterol synthesis reduces cisplatin-induced apoptosis, whereas silencing of LIPG, an enzyme involved in lipid metabolism, increases sensitivity to the drug.
Cholesterol Homeostasis Modulates Platinum Sensitivity in Human Ovarian Cancer.
Specimen part, Cell line
View SamplesA transgenic mouse was generated using a CD2-driven transgene containing the cDNA of Ppp2ca to achieve over-expression of PP2Ac in T cells. Nave CD4 T cells were isolated and lysed at times 0, 6, and 24 hours after stimulation with anti-CD3 and anti-CD28
Protein phosphatase 2A enables expression of interleukin 17 (IL-17) through chromatin remodeling.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Global transcriptome and chromatin occupancy analysis reveal the short isoform of GATA1 is deficient for erythroid specification and gene expression.
Specimen part, Cell line
View SamplesThe transcriptional activiy of GATA1s was compared to GATA1 through gene expression analysis in a cell line model with both erythroid and megakaryocyte differentiation.
Global transcriptome and chromatin occupancy analysis reveal the short isoform of GATA1 is deficient for erythroid specification and gene expression.
Specimen part, Cell line
View SamplesThe homeobox containing gene Arx is expressed during ventral telencephalon development and it is required for correct GABAergic interneuron tangential migration from the ganglionic eminences to the olfactory bulbs, cerebral cortex and striatum. Its human ortholog is associated with a variety of neurological clinical manifestations whose syntoms are compatible with a loss of cortical interneurons and altered basal ganglia related-activities in humans. Herein, we reported the identification by global expression profiling of a group of genes whose expression is consistently altered in Arx mutant ganglionic eminences. Following analysis revealed the striking ectopic expression in the ganglionic eminences of a number of genes normally not, or only marginally, expressed in the ventral telencephalon. Among them, we functionally analyzed Ebf3, whose ectopic expression in ventral telencephalon is preventingneuronal tangential migration. Further, we showed that Arx is sufficient to repress Ebf3 endogenous expression and that its silencing in Arx mutant tissue might marginally rescue tangential cell movements. Together, these data provide an initial analysis of the molecular pathways regulated by Arx and how their networking might regulate those specific cellular processes during telencephalon development strongly altered by loss of Arx.
Arx acts as a regional key selector gene in the ventral telencephalon mainly through its transcriptional repression activity.
No sample metadata fields
View SamplesEndometriosis is a complex pathological condition in which multiple components are involved in the disease development and clinical outcome. Endometriosis is mainly an inflammatory codition estrogen-dependent, with unknown pathogenesis, that is characterized by dissemination of edometrium tissue in ectopic position (ovary or pelvic peritoneum). Two main theories rise the pathologic onset: the presence of retrograde menstruation and celomic metaplasia in the pelvic peritoneum, that can occur for development defects. Endometriosis is related not only to genetic or immunological changes and to environmental pollution factors, as the endocrine interferents. The disease phenotype results from multiple events (genetics and enviromental), thus it is difficult to find a single gene as causative while is more probable that a gene network/s might involved in the onset and mantainement of the disease state. The peculiarity of endometriosis rely on the tissue speificity manteinance in the ectopic position, where it responds to the hormone stimuli as the tissue in the eutopic position.
Transcriptional profiling of endometriosis tissues identifies genes related to organogenesis defects.
Specimen part, Disease, Disease stage, Subject
View SamplesAdvanced 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.
Genes regulated by hepatocyte growth factor as targets to sensitize ovarian cancer cells to cisplatin.
Cell line
View Samplesp63 mutations have been associated with several human hereditary disorders characterized by ectodermal dysplasia such as EEC syndrome, ADULT syndrome and AEC syndrome . The location and functional effects of the mutations that underlie these syndromes reveal a striking genotype-phenotype correlation. Unlike EEC and ADULT that result from missense mutations in the DNA-binding domain of p63, AEC is solely caused by missense mutations in the SAM domain of p63. We report a study on the TAp63a isoform, the first to be expressed during development of the embryonic epithelia, and on its naturally occurring Q540L mutant derived from an AEC patient. To assess the effects of the Q540L mutation, we generated stable cell lines expressing TAp63a wt, DeltaNp63 alpha or the TAp63 alpha-Q540L mutant protein and used them to systematically compare the cell growth regulatory activity of the mutant and wt p63 proteins and to generate, by microarray analysis, a comprehensive profile of differential gene expression. We found that the Q540L substitution impairs the transcriptional activity of TAp63a and causes misregulation of genes involved in the control of cell growth and epidermal differentiation.
The Hay Wells syndrome-derived TAp63alphaQ540L mutant has impaired transcriptional and cell growth regulatory activity.
No sample metadata fields
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