Filters
Technology
Platform
GSE7345
Homo sapiens
8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The p21 RAS subfamily of small GTPases, including KRAS, HRAS, and NRAS, regulates cell proliferation, cytoskeletal organization and other signaling networks, and is the most frequent target of activating mutations in cancer. Activating germline mutations of KRAS and HRAS cause severe developmental abnormalities leading to Noonan, cardio-facial-cutaneous and Costello syndrome, but activating germline mutations of NRAS have not been reported. Autoimmune lymphoproliferative syndrome (ALPS) is the most common genetic disease of lymphocyte apoptosis and causes autoimmunity as well as excessive lymphocyte accumulation, particularly of CD4-, CD8- ab T cells. Mutations in ALPS typically affect CD95 (Fas/APO-1)-mediated apoptosis, one of the extrinsic death pathways involving tumor necrosis factor receptor (TNFR) superfamily proteins, but certain ALPS individuals have no such mutations. We show here that the salient features of ALPS as well as a predisposition to hematological malignancies can be caused by a heterozygous germline Gly13Asp activating mutation of the NRAS oncogene that does not impair CD95-mediated apoptosis. The increase in active, GTP-bound NRAS augments RAF/MEK/ERK signaling which markedly decreases the pro-apoptotic protein BIM and attenuates intrinsic, nonreceptor-mediated mitochondrial apoptosis. Thus, germline activating mutations in NRAS differ from other p21 Ras oncoproteins by causing selective immune abnormalities without general developmental defects. Our observations on the effects of NRAS activation indicate that RAS-inactivating drugs, such as farnesyl-transferase inhibitors (FTIs) should be examined in human autoimmune and lymphocyte homeostasis disorders.
Publication Title
NRAS mutation causes a human autoimmune lymphoproliferative syndrome.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Both environmental and genetic factors play important roles in the development of the metabolic syndrome. To elucidate how these factors interact under normal conditions, C57Bl/6 (B6) and 129S6/SvEvTac (129) mice were placed on a low-fat or high-fat diet. Liver samples were extracted and hybridized to Affymetrix Genome U74 (version 2) arrays.
Publication Title
Effects of diet and genetic background on sterol regulatory element-binding protein-1c, stearoyl-CoA desaturase 1, and the development of the metabolic syndrome.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
By using high-density DNA microarrays, we analyzed the gene-expression profile of liver biopsies from young and aged donors
Publication Title
Impairment of Host Liver Repopulation by Transplanted Hepatocytes in Aged Rats and the Release by Short-Term Growth Hormone Treatment.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 17 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The brain is the most cholesterol-rich organ in the body, most of which comes from in situ synthesis. Here we demonstrate that in insulin-deficient diabetic mice, there is a reduction in expression of the major transcriptional regulator of cholesterol metabolism, SREBP-2, and its downstream genes in the hypothalamus and other areas of the brain, leading to a reduction in brain cholesterol synthesis and synaptosomal cholesterol content. These changes are due, at least in part, to direct effects of insulin to regulate these genes in neurons and glial cells and can be corrected by intracerebroventricular injections of insulin. Knockdown of SREBP-2 in cultured neurons causes a decrease in markers of synapse formation and reduction of SREBP-2 in the hypothalamus of mice using shRNA results in increased feeding and weight gain. Thus, insulin and diabetes can alter brain cholesterol metabolism, and this may play an important role in the neurologic and metabolic dysfunction observed in diabetes and other disease states.
Publication Title
Diabetes and insulin in regulation of brain cholesterol metabolism.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Control and Liver Insulin Receptor KO mice (LIRKO) were sacrificed in the non-fasted state. RNA was prepared from liver samples and subjected to expression microarray analysis
Publication Title
Flavin-containing monooxygenase 3 as a potential player in diabetes-associated atherosclerosis.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Clariom S Assay (clariomsrat)
Description
TMAO is gut microbiota dependent metabolite catalyzed by monooxygenase FMO3 from TMA. TMAO is positively assocaited with different metabolic diseases such as diabetes, chronic kidney disease, and atherosclerosis.
Publication Title
Trimethylamine N-Oxide Binds and Activates PERK to Promote Metabolic Dysfunction.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
Illumina HiSeq 2000
Description
Tamoxifen (Nolvadex) is one of the most widely used and effective therapeutic agent for breast cancer. It benefits nearly 75% of patients with ER-positive breast cancer that receive this drug. Its effectiveness is mainly attributed to its capacity to function as an estrogen receptor (ER) antagonist, blocking estrogen binding sites on the receptor, and inhibiting the proliferative action of the receptor-hormone complex. Although, tamoxifen can induce apoptosis in breast cancer cells via upregulation of pro-apoptotic factors, it can also promote uterine hyperplasia in some women. Thus, tamoxifen as a multi-functional drug could have different effects on cells based on the utilization of effective concentrations or availability of specific co-factors. Evidence that tamoxifen functions as a GPR30 (G-Protein Coupled Receptor 30) agonist activating adenylyl cyclase and EGFR (Epidermal Growth Factor Receptor) intracellular signaling networks, provides yet another means of explaining the multi-functionality of tamoxifen. Here ordinary differential equation (ODE) modeling, RNA sequencing and real time qPCR analysis were utilized to establish the necessary data for gene network mapping of tamoxifen-stimulated MCF-7 cells, which express the endogenous ER and GPR30. The gene set enrichment analysis and pathway analysis approaches were used to categorize transcriptionally upregulated genes in biological processes. Of the 2,713 genes that were significantly upregulated following a 48 h incubation with 250 µM tamoxifen, most were categorized as either growth-related or pro-apoptotic intermediates that fit into the Tp53 and/or MAPK signaling pathways. Collectively, our results display that the effects of tamoxifen on the breast cancer MCF-7 cell line are mediated by the activation of important signaling pathways including Tp53 and MAPKs to induce apoptosis. Overall design: Gene expression analysis between tamoxifen-treated MCF-7 cells and untreated MCF-7 cells.
Publication Title
Tamoxifen-Induced Apoptosis of MCF-7 Cells via GPR30/PI3K/MAPKs Interactions: Verification by ODE Modeling and RNA Sequencing.
Sample Metadata Fields
Cell line, Subject
View Samples- Sus scrofa
- 6 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
Oocyte developmental potential is progressively obtained as females approach puberty. Therefore, oocytes derived from prepubertal females are less developmentally competent, indicated by decreased embryonic development, compared to oocytes derived from adult females.
Publication Title
Alterations in the transcriptome of porcine oocytes derived from prepubertal and cyclic females is associated with developmental potential.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
BMP4 is down-regulated in metastatic human and murine mammary tumours. Here we determined the effect of ectopic mouse Bmp4 re-expression on global gene expression patterns in orthotopic primary mammary tumours in syngeneic Balb/c mice.
Publication Title
BMP4 inhibits breast cancer metastasis by blocking myeloid-derived suppressor cell activity.
Sample Metadata Fields
Sex, Specimen part
View Samples- Ovis aries
- 15 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Expression data from Sheep longissimus dorsi (LD) muscle during development; fetal lambs (80, 100, 120 days gestation), new born lambs at birth (150 d) and lambs at 12 weeks (230 d)
Publication Title
A gene network switch enhances the oxidative capacity of ovine skeletal muscle during late fetal development.
Sample Metadata Fields
No sample metadata fields
View Samples