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GSE35206
Mus musculus
14 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The efficacy and exceptionally good tolerance of estrogen blockade in the treatment of breast cancer is well recognized but novel agents are required, especially to take advantage of the multiple consecutive responses obtained in breast cancer progressing following previous hormone therapy, thus delaying the use of cytotoxic chemotherapy with its usually serious side effects. Acolbifene (ACOL) is a novel and unique antiestrogen completely free of estrogen-like activity in both the mammary gland and uterus while preventing bone loss. From the preclinical and clinical data so-far available, this new antiestrogen represents a unique opportunity for a highly potent and specific blockade of estrogen action in the mammary gland and uterus while exerting estrogen-like beneficial effects in other tissues (selective estrogen receptor modulator or SERM activity). In order to better understand the specificity of action of acolbifene, we have used Affymetrix GeneChips containing 45,000 probe sets to analyze 34,000 genes to determine the specificity of this compound compared to the pure antiestrogen fulvestrant, as well as the mixed antagonists/agonists tamoxifen and raloxifene to block the effect of estradiol (E2) and to induce effects of their own on gene expression in the mouse mammary gland. The genes modulated by E2 were those identified in two separate experiments and validated by quantitative real-time PCR (Q_RT-PCR). Three hours after the single subcutaneous injection of E2 (0.05 ug), the simultaneous administration of acolbifene, fulvestrant, tamoxifen and raloxifene blocked by 98%, 62%, 43% and 92% the number of E2-upregulated genes, respectively. On the other hand, 70%, 10%, 25% and 55% of the genes down-regulated by E2 were blocked by the same compounds. Acolbifene was also the compound which, when used alone, modulated the smallest number of genes also influenced by E2, namely 4%, thus possibly explaining the potent tumoricidal action of this compound in human breast cancer xenografts where 61% of tumors disappeared, thus bringing a new paradigm in the hormonal therapy of breast cancer.
Publication Title
Specific transcriptional response of four blockers of estrogen receptors on estradiol-modulated genes in the mouse mammary gland.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Drosophila melanogaster
- 10 Downloadable Samples
- Drosophila Gene 1.0 ST Array (drogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Drosophila larvae fed palm fruit juice (PFJ) delay pupation via expression regulation of hormetic stress response genes linked to ageing and longevity.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Drosophila Gene 1.0 ST Array (drogene10st)
Description
PFJ (4 ml for a final concentration of 19,000 mg gallic acid equivalent (GAE) per kg diet or 0.86 mg GAE per kcal diet) was supplemented to larvae of fruit flies (Drosophila melanogaster) given a semi-purified diet to observe for possible effects on energy metabolism and lifespan. Larvae were used five days since the egg stage for gene expression studies. Results from the microarray data analysis carried out show that fruit fly larvae given PFJ had up-regulated transport and metabolic processes, while development and morphogenesis processes were down-regulated.
Publication Title
Drosophila larvae fed palm fruit juice (PFJ) delay pupation via expression regulation of hormetic stress response genes linked to ageing and longevity.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Drosophila melanogaster
- 4 Downloadable Samples
- Drosophila Gene 1.0 ST Array (drogene10st)
Description
PFJ (4 ml for a final concentration of 19,000 mg gallic acid equivalent (GAE) per kg diet or 0.86 mg GAE per kcal diet) was supplemented to larvae of fruit flies (Drosophila melanogaster) given a semi-purified diet to observe for possible effects on energy metabolism and lifespan. Fat bodies extracted from these larvae were used five days since the egg stage for gene expression studies. Results from the microarray data analysis carried out show that fruit fly larva fat bodies given PFJ had up-regulated heat shock protein genes, while cell cycle and growth genes were down-regulated.
Publication Title
Drosophila larvae fed palm fruit juice (PFJ) delay pupation via expression regulation of hormetic stress response genes linked to ageing and longevity.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 19 Downloadable Samples
- Illumina mouse-6 v1.1 expression beadchip
Description
Iron is an essential trace element whose absorption is usually tightly regulated in the duodenum. HFE-related hereditary hemochromatosis (HH) is characterized by abnormally low expression of the iron-regulatory hormone, hepcidin, which results in increased iron absorption. The liver is crucial for iron homeostasis as it is the main production site of hepcidin. The aim of this study was to explore and compare the genome-wide transcriptome response to Hfe deficiency and dietary iron overload in murine liver and duodenum.
Publication Title
Global transcriptional response to Hfe deficiency and dietary iron overload in mouse liver and duodenum.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Androgens have been postulated to be important modulators of adipose tissue metabolism and fat cell function. In the present study, we investigated the response of male and female mice retroperitoneal adipose tissue to the non-aromatizable androgen dihydrotestosterone (DHT). Adipose tissue samples were obtained in gonadectomized (GDX) animals treated with vehicle (control group), or injected with 0.1mg DHT at 1, 3, 6, 12, 18 and 24h prior to necropsy. Transcripts which were significantly modulated were considered as androgen-responsive genes. Quantitative real-time RT-PCR was used to confirm results from the microarry analysis in a subset of 46 probe sets in male mice and 98 probe sets in female mice. Using both methods and considering peak time versus control, 74.5% and 61.2% of the modulated genes were confirmed by PCR in males and females, respectively. Four genes were significantly stimulated in a similar manner by DHT in both sexes, namely metallothionein 1 (Mt1), growth arrest and DNA-damage-inducible 45 gamma (Gadd45g), cyclin-dependent kinase inhibitor 1A (Cdkn1a), and fk506-binding protein 5 (Fkbp5). All these genes appear to be associated with a down-regulation of adipocyte differentiation/proliferation and adipogenesis. In conclusion, this study which evaluated the transcriptome response of adipose tissue to DHT in male and female mice suggests that DHT consistently modulates genes involved in the regulation of adipogenesis in retroperitoneal adipose tissue of both male and female animals.
Publication Title
Response of the adipose tissue transcriptome to dihydrotestosterone in mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
Bone marrow mesenchymal stromal cells (MSCs) that express high levels of stem cell factor (SCF) and CXC chemokine ligand 12 (CXCL12) are one crucial component of the hematopoietic stem cell (HSC) niche. While the secreted factors produced by MSCs to support HSCs have been well described, little is known regarding the transcriptional regulators controlling the cell fate of MSCs and thus indirectly maintaining HSCs. Bmi1 is a polycomb group protein that regulates HSCs both cell intrinsically and extrinsically, but it is unknown in which cell type and how Bmi1 functions to maintain HSCs extrinsically. Here we show that Bmi1 maintains HSCs by preventing adipogenic differentiation of MSCs. Bmi1 is highly expressed in MSCs but becomes downregulated upon adipogenic differentiation and during aging. Deleting Bmi1 from MSCs increased marrow adipocytes, induced HSC quiescence and depletion, and impaired hematopoiesis. We found that Bmi1 repressed multiple developmental programs in MSCs by safeguarding the repressive epigenetic marks histone H2A ubiquitylation and H3 lysine 27 trimethylation. We identified a novel adipogenic program governed by Pax3, which Bmi1 repressed in MSCs. Our results establish Bmi1 as a critical regulator of MSC cell fate that suppresses marrow adipogenesis to create a supportive niche for HSCs. Overall design: RNA-Seq of two treatments (Ctrl, KO) with three replications per treatment.
Publication Title
Bmi1 Suppresses Adipogenesis in the Hematopoietic Stem Cell Niche.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 42 Downloadable Samples
- Illumina HiSeq 2500
Description
Transcriptome analysis was conducted on vorinostat resistant HCT116 cells (HCT116-VR) upon knockdown of potential vorinostat resistance candidate genes in the presence and absence of vorinostat. Potential vorinostat resistance candidate genes chosen for this study were GLI1 and PSMD13, which were identified through a genome-wide synthetic lethal RNA interference screen. To understand the transcriptional events underpinning the effect of GLI1 and PSMD13 knockdown (sensitisation to vorinostat-induced apoptosis), cells were first subjected to gene knockdown, then to treatment with vorinsotat or the solvent control. Two timepoints for drug treatment were assessed: a timepoint before induction of apoptosis (4hrs for siGLI1 and 8hrs for siPSMD13) and a timepoint when apoptosis could be detected (8hrs for siGLI1 and 12hrs for siPSMD13). Overall design: There are 42 samples in total, from triplicate independent biological experiments of 14 samples each.
Publication Title
A genome scale RNAi screen identifies GLI1 as a novel gene regulating vorinostat sensitivity.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Therapeutic hypothermia is a clinically effective treatment for various hypoxic and ischemic conditions, but the associated molecular mechanisms remain unclear. To gain insight into hypothermia-induced transcriptional response, mouse embryonic fibroblasts were exposed to mild hypothermia (32C) or normothermia (37C) for increasing time periods. We aimed to identify genes with temporally near-monotonic response as the most obvious candidates for mediating the therapeutic effects of hypothermia.
Publication Title
Estimating differential expression from multiple indicators.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
17-Estradiol (E2) is well known to be associated with uterine cancer, endometriosis, and leiomyomas. Although insulin-like growth factor I (IGF-I) has been identified as a mediator of the uterotrophic effect of E2 in several studies, this mechanism is still not well understood. In the present study, identification of the genes modulated by a physiological dose of E2, in the uterus, has been done in ovariectomized mice using Affymetrix microarrays. The E2-induced genomic profile shows that multiple genes belonging to the IGF-I pathway are affected after exposure to E2. Two phases of regulation could be identified. First, from 0 to 6 h, the expression of genes involved in the cell cycle, growth factors, protein tyrosine phosphatases, and MAPK phosphatases is quickly upregulated by E2, while IGF-I receptor and several genes of the MAPK and phosphatidylinositol 3-kinase pathways are downregulated. Later, i.e., from 6 to 24 h, transporters and peptidases/proteases are stimulated, whereas defense-related genes are differentially regulated by E2. Finally, cytoarchitectural genes are modulated later. The present data show that a physiological dose of E2 induces, within 24 h, a series of transcriptional events that promote the uterotrophic effect. Among these, the E2-mediated activation of the IGF-I pathway seems to play a pivotal role in the uterotrophic effect. Furthermore, the protein tyrosine phosphatases and MAPK phosphatases are likely to modulate the estrogenic uterotrophic action by targeting, at different steps, the IGF-I pathway.
Publication Title
Temporal analysis of E2 transcriptional induction of PTP and MKP and downregulation of IGF-I pathway key components in the mouse uterus.
Sample Metadata Fields
No sample metadata fields
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