KRAS mutations are the ost abundand driver mutations found in lung adenocarcinoma patients. Unfortunately, there are no clinical approved inhibitors available, to directly target mutant forms of KRAS. The aim of the study was to unravel the impact of upstream Egfr activation in signaling of mutated K-ras. We found that upregulation of G12D mutant Kras induced genes was significantly impaired when Egfr was knocked out. Our data suggests that signaling of mutant Kras depends on upstream activation. This finding may be exploited therapeutically by targeting EGFR in KRAS mutant patients. Overall design: We isolated mouse alveolar type II cells and induced the Kras G12D mutation, with and without concomitant Egfr knockout, in vitro. Cells lysates were analyzed 5 days following transgene induction.
JAK-STAT inhibition impairs K-RAS-driven lung adenocarcinoma progression.
Specimen part, Cell line, Subject
View SamplesThrough development of an in vivo orthotopic lung cancer model, we reveal an unanticipated pathway driving spontaneous metastasis that is orchestrated by the developmentally-regulated transcriptional repressor, Capicua (CIC). Overall design: RNAseq and DNA copy number analysis of H1975 (EGFR-mutant lung adenocarcinoma) cells in the context of drug resistance to rociletinib
Inactivation of Capicua drives cancer metastasis.
No sample metadata fields
View SamplesThe mechanisms underlying natural variation in lifespan and ageing rate remain largely unknown.
Transcriptome analysis of a long-lived natural Drosophila variant: a prominent role of stress- and reproduction-genes in lifespan extension.
Sex, Specimen part
View SamplesNonsense-mediated mRNA decay (NMD) is a molecular pathway of mRNA surveillance that ensures rapid degradation of mRNAs containing premature translation termination codons (PTCs) in eukaryotes. Originally, NMD was thought of as a quality control pathway that targets non-functional mRNAs arising from mutations and splicing errors. More recently, NMD has been shown to also regulate normal gene expression and NMD thus emerged as one of the key post-transcriptional mechanisms of gene regulation. We have now systematically analyzed the molecular mechanism of variable NMD efficiency and used different HeLa cell strains as a model system. The results of this analysis show that NMD efficiency can be remarkably variable and represents a stable characteristic of these strains. Low NMD efficiency is shown to be functionally related to the reduced abundance of the exon junction component RNPS1 in one of the HeLa strain analyzed. Furthermore, restoration of functional RNPS1 expression, but not of NMD-inactive mutant proteins, also restores efficient NMD in the RNPS1 deficient cell line. We conclude that cellular concentrations of RNPS1 modify NMD efficiency and propose that the cell type specific co-factor availability represents a novel principle that controls NMD.
The abundance of RNPS1, a protein component of the exon junction complex, can determine the variability in efficiency of the Nonsense Mediated Decay pathway.
Sex, Disease, Subject
View SamplesTranscriptional profiling of the zebrafish embryonic host response to a systemic bacterial infection with Salmonella typhimurium (strain SL1027); comparison between traf6 knock-down and control morpholino treated embryos. Overall design: All infection experiments were performed using mixed egg clutches of ABxTL strain zebrafish. Embryos injected with traf6 morpholino or a 5bp mismatch control morpholino were staged at 27 hours post fertilization (hpf) by morphological criteria and approximately 250 cfu of DsRed expressing Salmonella bacteria were injected into the caudal vein close to the urogenital opening. As a control an equal volume of PBS was likewise injected. Pools of 20-40 infected and control embryos were collected 8 hours post infection (hpi). The whole procedure was preformed in triplicate on separate days. Total RNA of the biological triplicates was pooled using equal amounts of RNA prior to RNAseq library preparation.
Transcriptome analysis of Traf6 function in the innate immune response of zebrafish embryos.
No sample metadata fields
View SamplesAdministration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extends the lifespan of various model organisms including yeast, flies and worms. In ageing yeast, spermidine treatment triggeres epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), leading to induction of autophagy and thereby suppressing oxidative stress and necrosis. In order to further characterize the effects by spermidine supplementation of aging yeast cultures and to understand how global histone deacetylation affects gene transcription during aging, Affymetrix-based microarray analyses of three day old as well as ten day old cultures with and without administration of spermidine was performed.
Induction of autophagy by spermidine promotes longevity.
Age, Compound, Time
View SamplesResponse to allergen was studied in epithelial cells derived from allergic pantients and from healthy controls. Cells were cultured after isolation from a nasal biopsy. Cells were exposed to Housed dust mite or vessel (saline)
Primary nasal epithelium exposed to house dust mite extract shows activated expression in allergic individuals.
No sample metadata fields
View SamplesIn order to identify transcriptional targets of ATF2, we used a recombinant adenovirus to express constitutively active ATF2 in murine hepatoblasts. Expression of GFP was the control condition.
JNK suppresses tumor formation via a gene-expression program mediated by ATF2.
Specimen part
View SamplesIn recent years, highly detailed characterization of adult bone marrow (BM) myeloid progenitors has been achieved and, as a result, the impact of somatic defects on different hematopoietic lineage fate decisions can be precisely determined. Fetal liver (FL) hematopoietic progenitor cells (HPCs) are poorly characterized in comparison, potentially hindering the study of the impact of genetic alterations on midgestation hematopoiesis. Numerous disorders, for example infant acute leukaemias, have in utero origins and their study would therefore benefit from the ability to isolate highly purified progenitor subsets. We previously demonstrated that a Runx1 distal promoter (P1)-GFP::proximal promoter (P2)-hCD4 dual-reporter mouse (Mus musculus) model can be used to identify adult BM progenitor subsets with distinct lineage preferences. In this study, we undertook the characterization of the expression of Runx1-P1-GFP and P2-hCD4 in FL. Expression of P2-hCD4 in the FL immunophenotypic Megakaryocyte-Erythroid Progenitor (MEP) and Common Myeloid Progenitor (CMP) compartments corresponded to increased granulocytic/monocytic/megakaryocytic and decreased erythroid specification. Moreover, Runx1-P2-hCD4 expression correlated with several endogenous cell surface markers' expression, including CD31 and CD45, providing a new strategy for prospective identification of highly purified fetal myeloid progenitors in transgenic mouse models. We utilized this methodology to compare the impact of the deletion of either total RUNX1 or RUNX1C alone and to determine the fetal HPCs lineages most substantially affected. This new prospective identification of FL progenitors therefore raises the prospect of identifying the underlying gene networks responsible with greater precision than previously possible. Overall design: mRNA profiles of single sorted Runx1 P2-hCD4+ Megakaryocyte Erythroid Progenitors (MEPs), Runx1 P2-hCD4- MEPs, Runx1 P2-hCD4+ Common Myeloid Progenitors (CMPs) and Runx1 P2-hCD4- CMPs from Mouse E14.5 Runx1 P2-GFP::P2-hCD4/+ Fetal Liver Samples
A novel prospective isolation of murine fetal liver progenitors to study in utero hematopoietic defects.
No sample metadata fields
View SamplesPlants are known to be responsive to volatiles, but knowledge about the molecular players involved in transducing their perception remain scarce.
WRKY40 and WRKY6 act downstream of the green leaf volatile E-2-hexenal in Arabidopsis.
Treatment
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