Filters
Technology
Platform
GSE33552
Homo sapiens
40 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Statins and bisphosponates (BPs) are two distinct classes of isoprenoid pathway inhibitors targeting HMG-CoA reductase (upstream enzyme) and Farnesyl-pyrophospate synthase (downstream enzyme) respectively. Here we conducted a comparative study of two representatives of these classes, fluvastatin (Fluva) and Zoledronate (Zol), to assess the differences in their in vivo metastatic potentials and pharmacogenomic profiles. Both drugs, being administered after emergence of detectable metastases, appeared to be potent metastasis inhibitors in MDA-MB-231 breast cancer metastasis model. We observed a reduced number of metastatic sites under Fluva, but not Zol treatment. Combinatorial in vivo treatment by Fluva and Zol showed no synergy for these drugs, as reported earlier on the basis of in vitro studies (Budman DR, Oncology 2006), staying in line with similarity of their transcriptomic profiles. Comparison of Zol and Fluva transcriptomic profiles revealed similar patterns of affected genes (describe involved genes functions) through different kinetics (when treated with IC50 determined for 72h treatment, the majority of changes were observed after 24h incubation with Fluva , and only after 48h incubation with Zol at 72h-IC50 or after 24h treatment with its 3 times higher dose). We demonstrated here that targeting different enzymes of the same pathway neither necessarily leads to distinct changes in gene profiles, nor to synergy for in vivo anti-metastatic potential.
Publication Title
Transcriptome analysis and in vivo activity of fluvastatin versus zoledronic acid in a murine breast cancer metastasis model.
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
To understand the link between invasion behavior and the steps of metastasis formation, we isolated invasive subpopulations from MDA-MB-231 cells in vitro using matrigel coated boyden chambers. Whole genome transcriptional profiling was used to characterize the expression changes uniquely related to invasive abilities of these cells.
Publication Title
Invading basement membrane matrix is sufficient for MDA-MB-231 breast cancer cells to develop a stable in vivo metastatic phenotype.
Sample Metadata Fields
Cell line
View Samples- Gallus gallus
- 4 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
Microarray analysis was performed on retina/RPE/choroid samples taken from the right eyes of male chicks across control and recovery from form deprivation conditions.
Publication Title
Pathway analysis identifies altered mitochondrial metabolism, neurotransmission, structural pathways and complement cascade in retina/RPE/ choroid in chick model of form-deprivation myopia.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Homo sapiens
- 12 Downloadable Samples
Illumina Genome Analyzer II
Description
Bromodomain extraterminal protein (BETP) inhibitors transcriptionally repress oncoproteins and NFkB target genes, which undermines the growth and survival of MCL cells. However, BETi treatment causes accumulation of BETPs, associated with reversible binding and incomplete inhibition of BRD4, which potentially compromises the activity of BETi in MCL cells. Unlike BETi, BET-PROTACs (proteolysis-targeting chimera) ARV-825 and ARV-771 (Arvinas, Inc.) recruit and utilize an E3-ubiquitin ligase to effectively degrade BETPs in MCL cells. BET-PROTACs induce more apoptosis than BETi of MCL cells, including those resistant to ibrutinib. BET-PROTAC treatment induced more perturbations in the mRNA and protein expressions than BETi, with depletion of c-Myc, CDK4, cyclin D1, and the NFkB transcriptional targets Bcl-xL, XIAP and BTK, while inducing the level of HEXIM1, NOXA and CDKN1A/p21. Treatment with ARV-771, which possesses superior pharmacological properties compared to ARV-825, inhibited the in vivo growth and induced greater survival improvement than the BETi OTX015 of immune-depleted mice engrafted with MCL cells. Co-treatment of ARV-771 with ibrutinib or the BCL2-antagonist venetoclax or CDK4/6 inhibitor palbociclib synergistically induced apoptosis of MCL cells. These studies highlight promising and superior pre-clinical activity of BET-PROTAC than BETi, requiring further in vivo evaluation of BET-PROTAC as a therapy for ibrutinib-sensitive or resistant MCL. Overall design: Twelve samples in biologic triplicates
Publication Title
BET protein proteolysis targeting chimera (PROTAC) exerts potent lethal activity against mantle cell lymphoma cells.
Sample Metadata Fields
Subject
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
One of the key aspects of neuronal differentiation is the array of neurotransmitters and neurotransmitter receptors that each neuron possesses. One important goal of developmental neuroscience is to understand how these differentiated properties are established during development. In this paper, we use fluorescence activated cell sorting and RNA-seq to determine the transcriptome of the Drosophila CNS midline cells, which consist of a small number of well-characterized neurons and glia. These data revealed that midline cells express 9 neuropeptide precursor genes, 13 neuropeptide receptor genes, and 31 small-molecule neurotransmitter receptor genes. In situ hybridization and high-resolution confocal analyses were carried-out to determine the midline cell identity for these neuropeptides and the neuropeptide receptors. The results revealed a surprising level of diversity. Neuropeptide genes are expressed in a variety of midline cell types, including motoneurons, GABAergic interneurons, and midline glia. These data revealed previously unknown functional differences among the highly-related iVUM neurons. There also exist segmental differences in expression for the same neuronal sub-type. Similar experiments on midline-expressed neuropeptide receptor genes reveal considerable diversity in synaptic inputs. Multiple receptor types were expressed in midline interneurons and motoneurons, and, in one case, link feeding behavior to gut peristalsis and locomotion. There were also segmental differences, variations between the 3 iVUMs, and three hormone receptor genes were broadly expressed in most midline cells. The Drosophila Castor transcription factor is present at high levels in iVUM5, which is both GABAergic and expresses the short neuropeptide F precursor gene. Genetic and misexpression experiments indicated that castor specifically controls expression of the short neuropeptide F precursor gene, but does not affect iVUM cell fate or expression of Gad1. This indicates a novel function for castor in regulating neuropeptide gene expression. Overall design: To study the development and differentiation of the CNS midline cells of Drosophila melanogaster on a genome-wide scale, these cells were labeled with GFP using the GAL/UAS system and FACS purified at 2 ermbryonic time-points; 6-8 hours and 14-16 hours after egg laying. Poly(A) mRNA was collected from these samples and cDNA libraries were generated. Sequencing was performed on 6 independent samples: Two FACS purified CNS-midline cell samples and one non-midline sample taken from 6-8 hours After Egg Laying (AEL) embryos and from 14-16 hours AEL embryos.
Publication Title
Transcriptome analysis of Drosophila CNS midline cells reveals diverse peptidergic properties and a role for castor in neuronal differentiation.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Research resource: progesterone receptor targetome underlying mammary gland branching morphogenesis.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Progesterone (P) acting through its cognate nuclear receptors (PRs) plays an essential role in driving pregnancy-associated branching morphogenesis of the mammary gland. However, the fundamental mechanisms, including global cistromic and acute genomic transcriptional responses that are required to elicit active branching morphogenesis in response to P, have not been elucidated. We used microarray analysis to identify global gene expression signatures that are acutely regulated by PRs in the mouse mammary gland after acute P treatment.
Publication Title
Research resource: progesterone receptor targetome underlying mammary gland branching morphogenesis.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 340 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
In our early study (PMID: 21939527), we have created a ClinicoMolecular Triad Classification (CMTC) to improve prediction and prognostication of breast cancer by using a training cohort contained 161 breast cancer patients (2003 to 2008). Here, a supplemental internal validation cohort contained 340 breast cancer patients was collected (2008 to 2010) for development of the CMTC.
Publication Title
Validation of the prognostic gene portfolio, ClinicoMolecular Triad Classification, using an independent prospective breast cancer cohort and external patient populations.
Sample Metadata Fields
Age, Disease stage
View Samples- Bos taurus
- 86 Downloadable Samples
- Illumina HiSeq 2000
Description
The transition between pregnancy and lactation is a major physiological change that dairy cows must contend with. Complex systemic and local processes involving gluconeogenesis, energy balance, utilisation of body reserves, insulin resistance and involution of the uterus can have an effect on animal health and farm profitability. Here we used an established Holstein cow model of fertility that displayed genetic and phenotypic divergence in calving interval, a trait used to define reproductive performance using a national breeding index in Ireland. Cows had similar genetic merit for milk production traits, but either very good genetic merit for fertility (‘Fert+’; n = 8) or very poor genetic merit for fertility (‘Fert-‘; n = 8). We investigated three distinct time-points, late pregnancy, early lactation and mid lactation (-18, 1 and 147 days on average with day 0 being birth), using RNA sequencing from both liver and muscle tissue biopsies and conducting a differential expression (DE) analysis. We found 807 and 815 unique genes to be DE in at least one time-point in liver and muscle respectively, of which 79% and 83% were only found in a single time-point; 40 and 41 genes were found DE at every time-point indicating possibly systemic or chronic dysregulation. Functional annotation resulted in evidence for two major physiological processes: immune and inflammation, and metabolic, lipid and carbohydrate-binding. These processes indicate areas of previous interest as well as specific systems that appear differentially regulated, and point towards interesting avenues of further research in a broad and complex field. Overall design: 96 samples total; 8 Fert+ (''high fertility''), 8 Fert- (''low fertility''); no controls; Fert+, Fert- differential gene expression at three timepoints in two tissues
Publication Title
Transcriptomics of liver and muscle in Holstein cows genetically divergent for fertility highlight differences in nutrient partitioning and inflammation processes.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Recent work suggests that imprinted genes may regulate the signalling function of the placenta by modulating the size of the endocrine compartment. Our work provides in vivo evidence that this hypothesis is well founded.
Publication Title
The imprinted Phlda2 gene modulates a major endocrine compartment of the placenta to regulate placental demands for maternal resources.
Sample Metadata Fields
Specimen part
View Samples