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.
Genes regulated by hepatocyte growth factor as targets to sensitize ovarian cancer cells to cisplatin.
Cell line
View SamplesThis experiment was carried out in the context of a study aimed to identify the function of the transcription facotrs HIF-1a in the pathogenesis of chronic lymphocytic leukemia (CLL).
HIF-1α regulates the interaction of chronic lymphocytic leukemia cells with the tumor microenvironment.
Sex, Cell line
View SamplesLiver gene expression was examined in male cynomolgus monkeys treated with ciprofibrate (PPAR-alpha agonist) for 4 days at 400 mg/kg/day and treated for 15 days at 0, 3, 30, 150 or 400 mg/kg/day. The untreated control group were given only the vehicle (0.5% hydroxypropyl methylcellulose). Two animals per group were used for the 4 day treatment and four animals per group were used for the 15 day treatment (except the 15 day control group, which had three animals). Selection of significantly changed probesets was done using Rosetta Resolver and the fold-change and p values as determined by Resolver are given below. Affymetrix CEL files and MAS5-processed data have been made availabe for convenience. Note that data processing reported in the Toxicological Sciences manuscript was done using Rosetta Resolver and the treated versus control group fold-change and p-value are appended to the Series entry. An article has been published in Toxicological Sciences regarding this dataset; the data interpretation was based on the Rosetta Resolver data.
Gene expression profiling of the PPAR-alpha agonist ciprofibrate in the cynomolgus monkey liver.
No sample metadata fields
View SamplesEffect of FGF2 on the transcriptional profile of microvascular endothelial cells
A pro-inflammatory signature mediates FGF2-induced angiogenesis.
Specimen part, Cell line, Compound
View SamplesHere we analyse single cell transcriptome profiles of EZH2-deficient human embroynic stem cells Overall design: Single cell transcriptome (mRNA-Seq) from Ezh2-/- (Null) and EZH2+/+ (WT) human ESC
Deletion of the Polycomb-Group Protein EZH2 Leads to Compromised Self-Renewal and Differentiation Defects in Human Embryonic Stem Cells.
Specimen part, Subject
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 SamplesThis SuperSeries is composed of the SubSeries listed below.
Distinct Gene Regulatory Pathways for Human Innate versus Adaptive Lymphoid Cells.
Specimen part
View SamplesInnate lymphoid cells (ILCs) serve as sentinels in mucosal tissues, sensing release of soluble inflammatory mediators, rapidly communicating danger via cytokine secretion, and functioning as guardians of tissue homeostasis. Although ILCs have been studied extensively in model organisms, little is known about these first responders in humans, especially their lineage and functional kinships to cytokine-secreting T helper cell (Th) counterparts. Here, we report gene regulatory circuitries for four human ILCTh counterparts derived from mucosal environments, revealing that each ILC subset diverges as a distinct lineage from Th and circulating natural killer cells, but shares circuitry devoted to functional polarization with their Th counterparts. Super-enhancers demarcate cohorts of cell identity genes in each lineage, uncovering new modes of regulation for signature cytokines, novel molecules that likely impart important functions to ILCs, and potential mechanisms for autoimmune disease SNP associations within ILCTh subsets.
Distinct Gene Regulatory Pathways for Human Innate versus Adaptive Lymphoid Cells.
Specimen part
View SamplesPressure overload-induced cardiac hypertrophy was examined in IL-18 knockout and littermate control mice.
Interleukin-18 knockout mice display maladaptive cardiac hypertrophy in response to pressure overload.
Specimen part
View SamplesThe 6-hydroxydopamine (6OHDA) rat model of parkinsonism is among the first, and most commonly used, animal models of Parkinsons disease. It provides insight into the compensatory changes that occur in the brain after dopamine (DA) neuron degeneration. In order to better define the consequences of substantia nigra DA neuron loss on the neural and glial populations during and following nigrostriatal degeneration, tissue was collected and evaluated from the substantia nigra of 6OHDA or vehicle treated, or nave rats at 1, 2, 4, 6 & 16 weeks.
The longitudinal transcriptomic response of the substantia nigra to intrastriatal 6-hydroxydopamine reveals significant upregulation of regeneration-associated genes.
Sex, Specimen part
View Samples