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GSE11729
Homo sapiens
2 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Controlled activation of epidermal growth factor receptor (EGFR) is systematically guaranteed at the molecular level, however aberrant activation of EGFR is frequently found in cancer. Transcription induced by EGFR activation often involves coordinated expression of genes that positively and negatively regulate the original signaling pathway, therefore alterations in EGFR kinase activity may reflect changes in gene expression associated with the pathway. In this study, we investigated transcriptional changes following EGF stimulation with or without the EGFR kinase inhibitor Iressa in H1299 human non-small-cell lung cancer cells (parental H1299, H1299 cells which overexpress wild-type: EGFR-WT and mutant EGFR: L858R). Our results clearly showed differences in transcriptional activity in the absence or presence of EGFR kinase activity, and genes sharing the same molecular functions showed distinct expression dynamics. The results showed particular enrichment of EGFR/ErbB signaling-related genes in a differentially expressed gene set, and significant protein expression of MIG6/RALT(ERRFI1), an EGFR negative regulator, was confirmed in L858R. High MIG6 protein expression was correlated with basal EGFR phosphorylation and inversely correlated with EGF-induced ERK phosphorylation levels. Investigation of NCI-60 cell lines showed that ERRFI1 expression was correlated with EGFR expression regardless of tissue type. These results suggest that cells accumulate MIG6 as an inherent negative regulator to suppress excess EGFR activity when basal EGFR kinase activity is considerably high. Taken together, an EGFR mutation can cause transcriptional changes to accommodate the activation potency of the original signaling pathway at the cellular level.
Publication Title
Mutation of epidermal growth factor receptor is associated with MIG6 expression.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Classification of Epstein-Barr virus-positive gastric cancers by definition of DNA methylation epigenotypes.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Aberrant promoter methylation is known to be deeply involved in human gastric carcinogenesis, while association of Epstein-Barr virus (EBV) to the aberrant methylation has not been fully clarified. We analyzed promoter methylation in clinical gastric cancer cases using illumina's Infinium beadarray, and hierarchical clustering analysis classified gastric cancer into three subgroups: low and high methylation epigenotypes in EBV-negative cases, and markedly higher methylation epigenotype that was completely matched to EBV-positive cases. Three epigenotypes were characterized by three groups of genes: genes methylated specifically in the EBV-positive epigenotype (EBV(+)-markers, e.g. CXXC4, TIMP2, PLXND1), genes methylated both in EBV-positive and high epigenotypes (High-markers, e.g. COL9A2, EYA1, ZNF365), and genes methylated all in EBV-positive, high and low epigenotypes of gastric cancer (Common-markers, e.g. AMPH, SORCS3, AJAP1). Polycomb repressive complex (PRC)-target genes in ES cells were significantly enriched in High- and Common-markers (P=2x10-15 and 2x10-34, respectively), but not in EBV(+)-markers (P=0.2), suggesting a different cause for EBV(+)-marker methylation. Recombinant EBV was infected to low epigenotype gastric cancer cell, MKN7. In all the three independently established clones, DNA methylation was induced in High- and EBV(+)-markers after 18 weeks, demonstrating that EBV-positive epigenotype should involve methylation of Common-, High-, and EBV(+)-markers simultaneously. The de novo methylated genes were overlapped well among the three clones, and the methylation caused gene repression. In summary, gastric cancer was classified into three DNA methylation epigenotypes, EBV-positive gastric cancer showed markedly high methylation epigenotype expanding to non-PRC target genes, and EBV infection per se could induce the EBV-positive epigenotype.
Publication Title
Classification of Epstein-Barr virus-positive gastric cancers by definition of DNA methylation epigenotypes.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Aberrant DNA methylation is induced at specific promoter CpG islands (CGIs) in contrast with mutations. The specificity is influenced by genome architecture and epigenetic factors, but their relationship is still unknown. In this study, we isolated promoter CGIs susceptible and resistant to aberrant methylation induction during prostate and breast carcinogenesis. The effect of genome architecture was more evident for promoter CGIs susceptible in both of the two tissues than for promoter CGIs susceptible only in one tissue. Multivariate analysis of promoter CGIs with tissue-nonspecific susceptibility showed that genome architecture, namely a remote location from SINE (OR=5.98; 95% CI=2.33-15.34) and from LINE (OR=2.08; 95% CI=1.03-4.21), was associated with increased susceptibility, independent of epigenetic factors such as the presence of RNA polymerase II (OR=0.09; 95% CI=0.02-0.48) and H3K27me3 (OR=3.28; 95% CI=1.17-9.21). These results showed that methylation susceptibility of promoter CGIs is determined both by genome architecture and epigenetic factors, independently.
Publication Title
Effects of genome architecture and epigenetic factors on susceptibility of promoter CpG islands to aberrant DNA methylation induction.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Recent clinical data suggest that the efficacy of statin treatment in patients with heart failure varies depending on the drugs administered. Therefore, the present study was undertaken to compare murine cardiac gene expression following treatment with four different statins.
Publication Title
Comparative effects of statins on murine cardiac gene expression profiles in normal mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Instructive mechanisms are present for induction of DNA methylation, as shown by methylation of specific CpG islands (CGIs) by specific inducers and in specific cancers. However, instructive factors involved are poorly understood, except for involvement of low transcription and trimethylation of histone H3 lysine 27 (H3K27me3). Here, we used methylated DNA immunoprecipitation (MeDIP) combined with a CGI oligonucleotide microarray analysis, and identified 5510 and 521 genes with promoter CGIs resistant and susceptible, respectively, to DNA methylation in prostate cancer cell lines. Expression analysis revealed that the susceptible genes had low transcription in a normal prostatic epithelial cell line. Chromatin immunoprecipitation with microarray hybridization (CHiP-chip) analysis of RNA polymerase II (Pol II) and histone modifications showed that, even among the genes with low transcription, the presence of Pol II was associated with marked resistance to DNA methylation (OR = 0.22; 95% CI = 0.12-0.38), and H3K27me3 was associated with increased susceptibility (OR = 11.20; 95% CI = 7.14-17.55). The same was true in normal human mammary epithelial cells for 5430 and 733 genes resistant and susceptible, respectively, to DNA methylation in breast cancer cell lines. These results showed that the presence of Pol II, active or stalled, and H3K27me3 can predict the epigenetic fate of promoter CGIs independently of transcription levels.
Publication Title
The presence of RNA polymerase II, active or stalled, predicts epigenetic fate of promoter CpG islands.
Sample Metadata Fields
Cell line
View Samples- Rattus norvegicus
- 8 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The effects of the administration of molecular hydrogen-saturated drinking water (hydrogen water) on hepatic gene expression were investigated in rats. Using DNA microarrays, 548 upregulated and 695 downregulated genes were detected in the liver after a 4-week administration of hydrogen water. Gene Ontology analysis revealed that genes for oxidoreduction-related proteins, including hydroxymethylglutaryl CoA reductase, were significantly enriched in the upregulated genes.
Publication Title
Hepatic oxidoreduction-related genes are upregulated by administration of hydrogen-saturated drinking water.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Rattus norvegicus
- 8 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Persimmon (Diospyros kaki L. f.) is a most popular fruit in Asian countries but its peels are totally wasted despite of containing a plenty of antioxidants such as carotenoids and polyphenols. We prepared a fat-soluble extract from a persimmon peel (PP) fraction and fed type 2 diabetic Goto-Kakizaki (GK) rats with a PP extract-containing AIN-93G diet (PP diet) for 12 weeks. Compared with the control AIN-93G diet, the feeding of the PP diet reduced the plasma glutamic-pyruvate transaminase activity significantly, with accumulation of -cryptoxanthin in the liver. A DNA microarray analysis revealed that the PP diet altered the hepatic gene expression profiles. In particular, insulin signaling pathway-related genes were significantly enriched in differentially expressed gene sets. Moreover, Western blotting analysis actually showed the promotion of IR tyrosine phosphorylation. All these data suggest that the PP extract administration to the GK rats improves their insulin resistance.
Publication Title
Hepatic gene expression of the insulin signaling pathway is altered by administration of persimmon peel extract: a DNA microarray study using type 2 diabetic Goto-Kakizaki rats.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
Illumina HiSeq 2000
Description
The inhibitor of DNA binding 2 (Id2) is essential for NK cell development with its canonical role in this pathway being to antagonize E-proteins, silencing E-box gene expression and subsequent commitment to the T and B cell lineages. However, how E-box genes prevent NK cell development and homeostasis remains enigmatic. Here we identify a key role for Id2 in regulating the threshold for IL-15 receptor signaling and homeostasis of NK cells by repressing multiple E-protein target genes including Socs3. Deletion of Id2 in mature NK cells was incompatible with their homeostasis due to impaired IL-15 receptor signaling. Id2-null NK cells displayed impaired IL-15 mediated JAK1/STAT5 phosphorylation, compromised metabolic function and enhanced apoptosis. Remarkably, Id2-null NK cell homeostasis could be fully rescued in vivo by IL-15 receptor stimulation and partially rescued by genetic ablation of Socs3. During normal NK cell maturation we observed an inverse correlation between the expression levels of E-protein target genes and Id2. These results shift the current paradigm on the role of Id2, indicating that it is not only required to antagonize E-proteins during NK cell commitment, but constantly required to titrate E-protein activity to regulate NK cell fitness and responsiveness to IL-15. Overall design: Transcriptional profiling of wild type and Id2-null natural killer (NK) cells using RNA sequencing
Publication Title
The Helix-Loop-Helix Protein ID2 Governs NK Cell Fate by Tuning Their Sensitivity to Interleukin-15.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Rattus norvegicus
- 36 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Although various mechanisms have been inferred for combinatorial actions of multiple carcinogens, these mechanisms have not been well demonstrated in experimental carcinogenesis models. We evaluated mammary carcinogenesis initiated by combined exposure to various doses of radiation and chemical carcinogens. Female rats at 7 weeks of age were -irradiated (0.22 Gy) and/or exposed to 1-methyl-1-nitrosourea (20 or 40 mg/kg, single intraperitoneal injection) or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (40 mg/kg/day by gavage for 10 days) and were observed until 50 weeks of age. The incidence of mammary carcinoma increased steadily as a function of radiation dose in the absence of chemicals; mathematical analysis supported an additive increase when radiation was combined with a chemical carcinogen, irrespective of the chemical species and its dose. Hras mutations were characteristic of carcinomas that developed after chemical carcinogen treatments and were overrepresented in carcinomas induced by the combination of radiation and MNU (but not PhIP), indicating an interaction of radiation and MNU at the level of initiation. The expression profiles of seven classifier genes, previously shown to distinguish two classes of rat mammary carcinomas, categorized almost all examined carcinomas that developed after individual or combined treatments with radiation (1 Gy) and chemicals as belonging to a single class; more comprehensive screening using microarrays and a separate test sample set failed to identify differences in gene expression profiles among these carcinomas. These results suggest that a complex, multilevel interaction underlies the combinatorial action of radiation and chemical carcinogens in the experimental model.
Publication Title
Molecular characterization of cancer reveals interactions between ionizing radiation and chemicals on rat mammary carcinogenesis.
Sample Metadata Fields
Specimen part
View Samples