GIST is considered to invariably arise through gain-of-function KIT or PDGFRA mutation of the interstitial cells of Cajal (ICC). However, the genetic basis of the malignant progression of GIST is poorly understood.
Distinct gene expression-defined classes of gastrointestinal stromal tumor.
Sex, Age
View SamplesAlthough EWS/FLI-1 fusion protein is responsible for most Ewings sarcoma family tumors (ESFT), the function of native EWS remains largely unknown. Here, we first showed that EWS repressed protein expression in a tethering assay. mRNAs bound to EWS were determined by RNA-immunoprecipitation Chip assay, and one of them, proline-rich Akt substrate of 40 kDa (PRAS40) mRNA, directly interacted with EWS. The inhibitor of AKT, API-2, repressed ESFT cell proliferation. We demonstrate that EWS negatively regulated PRAS40 protein expression through binding to PRAS40 3UTR. Furthermore, PRAS40 knockdown inhibited the proliferation and metastatic potential of ESFT cells.
PRAS40 is a functionally critical target for EWS repression in Ewing sarcoma.
Cell line
View SamplesThe demyelination (dmy) rat is a unique spontaneous myelin mutation that exhibits severe myelin breakdown with a late onset of clinical signs. The causative autosomal recessive mutation has been identified at the MRS2 magnesium transporter (Mrs2) gene, which encodes an essential component of the major Mg2+ influx system in mitochondria.
Enhanced Expression of Trib3 during the Development of Myelin Breakdown in dmy Myelin Mutant Rats.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of a new pathway for Th1 cell development induced by cooperative stimulation with IL-4 and TGF-β.
Specimen part
View SamplesIL-4 plays an important role in the induction of Th2 and Th9 cells as well as in the inhibition of Th1 cell generation. We herein show that a combination of IL-4 and TGFbeta augment the development of Th1 cells that express CD103 (CD103+ Th1 cells) if IFNgamma is present. The T-box containing transcription factor, eomesodermin (Eomes) is preferentially expressed in CD103+ Th1 cells, and is involved in IFNgamma production. The induction of T-bet during early T cell activation is essential for the formation of the active chromatin at both the Eomes and IFNgamma gene loci. TGFbeta is required for the induction of Eomes and CD103, as well as the inhibition of Th2 cytokine expression. In addition, IL-4 induces Eomes transcription through activation of the Stat6 signaling pathway. IFNgamma-producing CD103+ Th1 cells are detected in the IEL of normal mice, and their numbers significantly decrease in Tbet- and Stat6-deficient mice. These results represent the first molecular mechanism of IL-4/TGFbeta-dependent augmentation of Th1 cell generation, and raise the possibility that IL-4 and TGFbeta may simultaneously enhance the Th1 cell-mediated immune responses under certain cytokine conditions.
Identification of a new pathway for Th1 cell development induced by cooperative stimulation with IL-4 and TGF-β.
Specimen part
View SamplesGene expression was examined in granulosa cells and oocytes in various stage of follicle and in vitro grown oocytes and granulosa cells complexes in sus scrofa.
Gene expression patterns in granulosa cells and oocytes at various stages of follicle development as well as in in vitro grown oocyte-and-granulosa cell complexes.
Specimen part
View SamplesUsing Affymetrix HG-U133-Plus 2.0 array and Laser Capture Microdissection techniques, we determined whether growth in different zones of the same tumor affected expression of genes by human pancreatic cancer cells. Human L3.6pl pancreatic cancer cells were implanted into the pancreas of nude mice. Gene expression patterns in tumor cells within the central and peripheral zones were compared and statistical differences were determined for 1222 genes. Bioinformatic functional prediction analysis revealed that 346 upregulated genes in the peripheral zone were related to cytoskeleton organization and biogenesis, cell cycle, cell adhesion, cell motility, DNA replication, localization, integrin-mediated signaling pathway, development, morphogenesis, and IkB kinase/NF-kB cascade; and 876 upregulated genes in the central zone were related with regulation of cell proliferation, regulation of transcription, transmembrane receptor protein tyrosine kinase signaling pathway, response to stress, small GTPase mediated signal transduction, hexose metabolism, cell death, response to external stimulus, carbohydrate metabolism, and response to wounding. Results from the microarray were confirmed for reliability by in situ hybridization analysis. Collectively, these data demonstrate zonal heterogeneity for gene expression profiles in tumors and suggest that characterization of zonal gene expression profiles are essential to obtain reproducible data, to predict disease prognosis, and to design specific therapeutics.
Zonal heterogeneity for gene expression in human pancreatic carcinoma.
No sample metadata fields
View SamplesWe used microarray analysis to identify specific molecular mechanisms controlling IL-5 transcription in memory Th2 cells.
Eomesodermin controls interleukin-5 production in memory T helper 2 cells through inhibition of activity of the transcription factor GATA3.
Specimen part
View SamplesThe gut microbiota is essential for several aspects of host physiology such as metabolism, epithelial barrier function and immunity. Previous studies have revealed that host immune system as well as diet and other environmental factors have a strong impact on the composition and activity of gut microbiota, but the molecular requirements for such functional regulation remain unknown. We show that the bacteria belonging to phylum Bacteroidetes acquire their symbiotic activity in the colonic mucus, depending on a newly characterized molecular family encoded within the polysaccharide utilization loci (PUL), which we have named Mucus-Associated Functional Factor (MAFF).
IgA regulates the composition and metabolic function of gut microbiota by promoting symbiosis between bacteria.
Sex, Specimen part
View SamplesAlveolar macrophages (AMs) of Bach2 KO mice show multiple alternations in their functions including lipid metabolism. We aimed to clarify the mechanism whereby deficiency of Bach2 impairs the function of AMs and ruins the homeostasis of lungs. Now we report that some cytokines produced from Bach2-deficient T cells alter the character of AMs and expression of Bach2 is necessary for AMs to maintain the function of lipid metabolism. Overall design: mRNA profiling of AMs from 16-week old control mice, Bach2-floxed CD4cre mice, WT mice and Bach2 germline KO mice were examined by deep sequencing using HiSeq2500. Please note that two macrophage populations observed in Bach2-floxed/CD4-cre cKO mice were analyzed; One with normal surface marker phenotype that was the same as control mice (normal). The other with aberrant surface marker phenotype compared with control mice (abnormal).
Inflammatory responses induce an identity crisis of alveolar macrophages, leading to pulmonary alveolar proteinosis.
Sex, Specimen part, Subject
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