Interferons have been ascribed to mediate antitumor effects. IRF-1 is a major target gene of interferons. It inhibits cell proliferation and oncogenic transformation. Here we show that 60% of all mRNAs deregulated by oncogenic transformation mediated by c-myc and H-ras are reverted to the expression levels of non-transformed cells by IRF-1. These include cell cycle regulating genes. Activation of IRF-1 decreases cyclin D1 expression and CDK4 kinase activity concomitant with dephosphorylation of pRb. These effects of IRF-1 are mediated by inhibition of the MEK-ERK pathway and a transcriptional repression of cyclin D1. IRF-1 mediated effects on cell cycle progression were found to be overridden by ectopic expression of cyclin D1. Ablation of cyclin D1 by RNA interference experiments prevents transformation and tumor growth in nude mice. The data demonstrate that cyclin D1 is a key target for IRF-1 mediated tumor suppressive effects.
Tumor suppression by IFN regulatory factor-1 is mediated by transcriptional down-regulation of cyclin D1.
Specimen part
View SamplesRhoB null mice show decreases in pathological angiogenesis in the ischemic retina and reduces angiogenesis in response to cutaneous wounding, but enhances lymphangiogenesis following both dermal wounding and inflammatory challenge.
RhoB controls coordination of adult angiogenesis and lymphangiogenesis following injury by regulating VEZF1-mediated transcription.
Sex, Specimen part
View SamplesNuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that induces a battery of cytoprotective genes in response to oxidative/electrophilic stress. Kelch-like ECH associating protein 1 (Keap1) sequesters Nrf2 in the cytosol. The purpose of this study was to investigate the role of Nrf2 in regulating the mRNA of genes encoding drug metabolizing enzymes and xenobiotic transporters. Microarray analysis was performed in livers of Nrf2-null, wild-type, Keap1-knockdown mice with increased Nrf2 activation, and Keap1-hepatocyte knockout mice with maximum Nrf2 activation. In general, Nrf2 did not have a marked effect on uptake transporters, but the mRNAs of organic anion transporting polypeptide 1a1, sodium taurocholate cotransporting polypeptide, and organic anion transporter 2 were decreased with Nrf2 activation. The effect of Nrf2 on cytochrome P450 (Cyp) genes was minimal, with only Cyp2a5, Cyp2c50, Cyp2c54, and Cyp2g1 increased, and Cyp2u1 decreased with enhanced Nrf2 activation. However, Nrf2 increased mRNA of many other phase-I enzymes, such as aldo-keto reductases, carbonyl reductases, and aldehyde dehydrogenase 1. Many genes involved in phase-II drug metabolism were induced by Nrf2, including glutathione S -transferases, UDP- glucuronosyltransferases, and UDP-glucuronic acid synthesis enzymes. Efflux transporters, such as multidrug resistance-associated proteins, breast cancer resistant protein, as well as ATP-binding cassette g5 and g8 were induced by Nrf2. In conclusion, Nrf2 markedly alters hepatic mRNA of a large number of drug metabolizing enzymes and xenobiotic transporters, and thus Nrf2 plays a central role in xenobiotic metabolism and detoxification.
Effect of graded Nrf2 activation on phase-I and -II drug metabolizing enzymes and transporters in mouse liver.
Sex, Age, Specimen part
View SamplesAll mRNA was isolated after 8 hours of culture time in each of three culture conditions. (1) TCPS Plate, (2) Collagen-GAG 2 dimensional coated plate and (3) collagen-GAG three dimensional mesh.
Fibroblast remodeling activity at two- and three-dimensional collagen-glycosaminoglycan interfaces.
No sample metadata fields
View SamplesThe goal of this study was to investigate the effects of vairous diets on the expression of genes involved in intermediary metabolism in liver. Adult wild type male mice (3 for each group) were fed with the corresponding diet for two weeks, and then liver samples were collected. Total RNA was isolated by the RNAzol B reagent, and pellet was disolved in DEPC-treated water. Total RNA was isolated using RNA Bee reagent (Tel-Test Inc., Friendswood, TX) per the manufacturers protocol. RNA concentrations were quantified using a NanoDrop Spectrophotometer (NanoDrop Technologies, Wilmington, DE) at a wavelength of 260 nm. The integrity of the total RNA samples was evaluated by formaldehyde-agarose gel electrophoresis, and confirmed by visualization of 18S and 28S rRNA bands. The gene expression was determined by Affymetrix Mouse 430 2.0 Gene Expression Microarray. Nine different diets were used: Diet 1. TD.84224. EFA Deficient diet; Diet 2. TD 97070. High fat diet: Diet 3. TD.88137. Adjusted Calories Diet (42% from fat) (Western Diet); Diet 4. TD.02028. Atherogenic Rodent Diet; Diet 5. TD.89247. 60% Fructose Diet; Diet 6. TD.94048. AIN-93M Purified Diet, Diet 7. Current rodent diet used in LAR; Diet 8. DHA-supplemented diet; Diet 9. Diet-restriction: 75% of the diet consumed by ad lib feeding. Mice (n=3/diet) were fed one of these diets (Harlan Laboratories) for 3 weeks. All mice were euthanized in the morning (8:0010:00 A.M.) and blood and tissue samples were collected. All procedures were approved in accordance with Institutional Animal Care and Use Committee guidelines.
Effect of diet on expression of genes involved in lipid metabolism, oxidative stress, and inflammation in mouse liver-insights into mechanisms of hepatic steatosis.
Sex, Age, Specimen part
View SamplesTo understand molecular mechanisms by which reducing Id2 rescues impaired erythropoiesis and hematopoietic progenitor cell development in Gfi-1-/- mice, we compared gene expression in Gfi-1-/-;Id2+/- and Gfi-1-/- BMC using Affymetrix microarray.
Gfi-1 regulates the erythroid transcription factor network through Id2 repression in murine hematopoietic progenitor cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A systems analysis identifies a feedforward inflammatory circuit leading to lethal influenza infection.
Sex, Specimen part
View SamplesTranscriptomic comparison of 5 cell types during lethal and non-lethal influenza infection and further use of these signatures in a top-down systems analysis investigating the relative pathogenic contributions of direct viral damage to lung epithelium vs. dysregulated immunity during lethal influenza infection.
A systems analysis identifies a feedforward inflammatory circuit leading to lethal influenza infection.
Sex, Specimen part
View SamplesTranscriptome of murine testis from wild type mice and mice lacking telomerase for three generations (G3-Terc), Ku86 or both telomerase and Ku86.
Effectors of mammalian telomere dysfunction: a comparative transcriptome analysis using mouse models.
No sample metadata fields
View SamplesClinicians need additional metrics for predicting quality of human oocytes for IVF procedures. Human polar bodies reflect the oocyte transcript profile. Quantitation of polar body mRNAs could allow for both oocyte ranking and embryo preferences in IVF applications. The transcriptome of a polar body has never been reported, in any organism. Overall design: Eight total samples. There are 2 biological replicates of the following four conditions: pooled oocytes and their sister polar bodies and a single oocyte and its sister polar body.
The transcriptome of a human polar body accurately reflects its sibling oocyte.
Specimen part, Subject
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