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.
Mutation of epidermal growth factor receptor is associated with MIG6 expression.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide screen of cell-cycle regulators in normal and tumor cells identifies a differential response to nucleosome depletion.
Specimen part, Cell line
View SamplesGene-expression in siRNA treated U2OS and hTERT-RPE1 cells showed that CASP8AP2, NPAT and HINFP do not regulate expression of each other, and do not have any common target genes, except histones. Most histone genes are downregulated in U2OS cells following loss of CASP8AP2, NPAT or HINFP. In normal cells, highly-expressed histone genes were downregulated, albeit less than in tumor cells following loss of CASP8AP2. The p53 target genes were upregulated relatively late, clearly after the changes in expression of histone genes were observed.
Genome-wide screen of cell-cycle regulators in normal and tumor cells identifies a differential response to nucleosome depletion.
Cell line
View SamplesTF binding clusters in promoter correlate well with gene expression. We used ChIP-seq to map binding sites of the majority of highly expressed TFs in the cell. The size of clusters of TFs in the promoters of genes were found to correlate well with gene expression.
Transcription factor binding in human cells occurs in dense clusters formed around cohesin anchor sites.
Cell line
View SamplesGene expression profiles of 10 uterine leiomyomas and their matched normal myometrium specimens were studied using Affymetrix GeneChip Human Genome U133 Plus 2.0 gene expression arrays. Four tumors displayed a codon 44 mutation, four carried a intron 1 mutation, and the remaining two displayed no MED12 mutation.
MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas.
Specimen part, Subject
View SamplesTo identify downstream targets of Jak/Stat3 pathways without being distracted by differentiation signalings from MEK/ERK pathway, we exploited a engineered B6 cells, which stably stably expressing a chimeric receptor (GRgp-Y118F). The chimeric receptor can induce the phosphorylation of Stat3 by GCSF without activating the MEK/ERK pathway. To mimic the effect of GCSF, the chimeric B6 cells were also treated with LIF plus a selective MEK chemical inhibitor, PD0325901, to induce LIF/Jak/Stat3 but MEK/ERK pathways.
Gbx2, a LIF/Stat3 target, promotes reprogramming to and retention of the pluripotent ground state.
Cell line
View SamplesAnalysis of ovarian cancer cell lines after knockdown of FGFRL1 using SiRNA.
FGFRL1 Promotes Ovarian Cancer Progression by Crosstalk with Hedgehog Signaling.
Cell line
View SamplesAnalyze the effect of TLR9 deficiency on immue cell function at the gene expression level. Our hypothesis was that TLR9 deficiency promotes CD73 expression in T cells thus regulates autoimmune diabetes development in NOD mice.
TLR9 deficiency promotes CD73 expression in T cells and diabetes protection in nonobese diabetic mice.
Specimen part
View SamplesA data set of normal epithelium, serous ovarian surface epithelial-stromal tumors (benign and type II malignancies), stroma distal to tumor, and stroma adjacent to tumor (50 samples total). Additional cel files are included which represent replicate sampling from patients, and cel files that failed quality control but may be bioinformatically interesting. Additional replicate or failed cel files were not included in the final analysis (and so these samples were not included in the matrix).
Dysregulation of AKT3 along with a small panel of mRNAs stratifies high-grade serous ovarian cancer from both normal epithelia and benign tumor tissues.
Specimen part, Subject
View SamplesIrradiation induced bone marrow ablation ultimately enhanced PTH anabolic effects in bone.
An irradiation-altered bone marrow microenvironment impacts anabolic actions of PTH.
Specimen part, Treatment
View Samples