TIMP-4 overexpression increases tumor burden in mice, promotes progenitor cell phenotype and sensitizes cells to apoptosis, by relying on NFkB signaling
Tissue inhibitor of metalloproteinases-4 (TIMP-4) regulates stemness in cervical cancer cells.
Specimen part, Cell line
View SamplesINTRODUCTION: CDKN2A (p16) inactivation is common in lung cancer and occurs via homozygous deletions, methylation of promoter region, or point mutations. Although p16 promoter methylation has been linked to KRAS mutation and smoking, the associations between p16 inactivation mechanisms and other common genetic mutations and smoking status are still controversial or unknown. METHODS: We determined all three p16 inactivation mechanisms with the use of multiple methodologies for genomic status, methylation, RNA, and protein expression, and correlated them with EGFR, KRAS, STK11 mutations and smoking status in 40 cell lines and 45 tumor samples of primary non-small-cell lung carcinoma. We also performed meta-analyses to investigate the impact of smoke exposure on p16 inactivation. RESULTS: p16 inactivation was the major mechanism of RB pathway perturbation in non-small-cell lung carcinoma, with homozygous deletion being the most frequent method, followed by methylation and the rarer point mutations. Inactivating mechanisms were tightly correlated with loss of mRNA and protein expression. p16 inactivation occurred at comparable frequencies regardless of mutational status of EGFR, KRAS, and STK11, however, the major inactivation mechanism of p16 varied. p16 methylation was linked to KRAS mutation but was mutually exclusive with EGFR mutation. Cell lines and tumor samples demonstrated similar results. Our meta-analyses confirmed a modest positive association between p16 promoter methylation and smoking. CONCLUSION: Our results confirm that all the inactivation mechanisms are truly associated with loss of gene product and identify specific associations between p16 inactivation mechanisms and other genetic changes and smoking status.
Molecular portraits of epithelial, mesenchymal, and hybrid States in lung adenocarcinoma and their relevance to survival.
Sex, Age, Race
View SamplesOT-1 Transgenic CD8 T-cells were isolated from spleens of WT, PKC theta KO, and p50 cRel DKO mice. The T-cells were either cultured with non-pulsed DC (WT only and signified as "WT - UN") or with BMDCs pulsed with the OVA peptide SIINFEKL (N4) (WT, PKC theta KO, and p50 cRel DKO and signified as 'genotype - N4') at a ratio of 1:10 (DC:T-cell) for 18 hours. DCs then were depleted from the culture and RNA was made from the T-cells to measure gene expression at the early / late stage of T-cell activation
NF-κB is crucial in proximal T-cell signaling for calcium influx and NFAT activation.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Quantitative analysis of protein interaction network dynamics in yeast.
No sample metadata fields
View SamplesTo understand the principles underlying protein-protein interaction (PPI) complex changes in response to external perturbations, we created a highly multiplexed version of the murine dihydrofolate reductase protein complementation assay (mDHFR PCA) in Saccharomyces cerevisiae, allowing quantitative PPI complex profiling in vivo. We investigated the effects of 14 different conditions (including small molecules, abiotic stress factors, and nutrient composition) on a total of 1383 PPIs. More than half of PPIs (758) were found to be variable, and their Gene Ontology (GO) annotations were found to be informative of both the nature of the perturbation within each condition, as well as the overall variability of the interactions across conditions. Many perturbations triggered network changes characterized by large connected modules centered around highly connected proteins ('hubs'), suggesting that cellular control of a few proteins (e.g., by mRNA levels) can induce widespread PPI remodeling. Under a diauxic shift from glucose to ethanol as the main carbon source, we found a striking relationship between PPI changes measured by our assay and those predicted by mRNA expression under a simple law of mass action based model.
Quantitative analysis of protein interaction network dynamics in yeast.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
DIDO as a Switchboard that Regulates Self-Renewal and Differentiation in Embryonic Stem Cells.
Specimen part
View SamplesTransition from symmetric to asymmetric cell division requires precise coordination of differential gene expression. Embryonic stem cells (ESC) strongly express Dido3, whose C-terminal truncation impedes ESC differentiation while retaining self-renewal. We show that Dido3 binds to its gene locus via H3K4me3 and RNA pol II and, at differentiation onset, induces expression of its splice variant Dido1, which then leads to Dido3 degradation and downregulation of stemness genes. We propose that Dido isoforms act as a switchboard to regulate genetic programs for ESC transition from pluripotency maintenance to promotion of differentiation.
DIDO as a Switchboard that Regulates Self-Renewal and Differentiation in Embryonic Stem Cells.
Specimen part
View SamplesWe used Affymetrix expression arrays to determine changes in gene expression associated with activation of human NK cells mediated through treatment with cytokines IL-2, IL-12 and IL-18 over a 24 hour period.
PRDM1/Blimp-1 controls effector cytokine production in human NK cells.
Sex, Age, Specimen part
View SamplesEffect of NF-kB inhibition and activation on gene expression in mouse and human lung cancer cell-lines.
Lung tumor NF-κB signaling promotes T cell-mediated immune surveillance.
Cell line
View SamplesSenescent human fibroblasts were compared to young proliferating fibroblasts. Five different cell lines were compared. Illumina sequencing (HiSeq2000) was applied to generate 50bp single-end reads. Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de) Overall design: 48 samples: 3 biological replicates for each group: young proliferating and senescent BJ cells; young proliferating and senescent Wi-38 cells; young proliferating and senescent IMR-90 cells; 5 population doubling from young proliferating to senescent cell for HFF and MRC-5 cells
Conserved Senescence Associated Genes and Pathways in Primary Human Fibroblasts Detected by RNA-Seq.
No sample metadata fields
View Samples