The oncogenic mechanisms and tumour biology underpinning Clear Cell Sarcoma of Kidney (CCSK), the second commonest paediatric renal malignancy, are poorly understood and currently therapy depends heavily on Doxorubicin with cardiotoxic side-effects. Previously, we characterised the balanced t(10;17)(q22;p13) chromosomal translocation, identified at that time as the only recurrent genetic aberration in CCSK. This translocation results in an in-frame fusion of the YWHAE (encoding 14-3-3e) and NUTM2 genes, with a somatic incidence of 12%. Clinico-pathological features of that cohort suggested that this aberration might be associated with higher stage and grade disease. Since no primary CCSK cell line exists, we generated various stably transfected cell lines containing doxycycline-inducible HA-tagged-YWHAE-NUTM2, in order to study the effect of expressing this transcript. 14-3-3e-NUTM2-expressing cells exhibited significantly greater cell migration compared to mock-treated controls. Gene and protein expression studies conducted in parallel on this model system suggested dysregulation of signalling pathways as a basis to the migration changes. Importantly, by blocking these signalling pathways using anti-EGFR, anti-IGF1R and anti-PDGFa neutralising antibodies, the migratory advantage conferred by transcript expression was abrogated. These results support 14-3-3e-NUTM2 expression as a contributor to CCSK tumorigenesis and provide avenues for the exploration of novel therapeutic approaches in CCSK.
Dysregulated mitogen-activated protein kinase signalling as an oncogenic basis for clear cell sarcoma of the kidney.
Disease, Cell line
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Tribbles 3: a novel regulator of TLR2-mediated signaling in response to Helicobacter pylori lipopolysaccharide.
Specimen part, Cell line
View SamplesThis study set out to identify global changes in gene expression in human embryonic kidney (HEK) cells stably transfected with Toll-like receptor 2 (TLR2) over a 48 hour time-course, following stimulation with 10 g/ml lipopolysaccharide (LPS) from the gastric pathogen H. pylori.
Tribbles 3: a novel regulator of TLR2-mediated signaling in response to Helicobacter pylori lipopolysaccharide.
Specimen part
View SamplesPhotoreceptor disorders are collectively known as retinal degeneration (RD), and include retinitis pigmentosa (RP), cone-rod dystrophy and age related macular degeneration (AMD). These disorders are largely genetic in origin; individual mutations in any one of >200 genes cause RD, making mutation specific therapies prohibitively expensive. A better treatment plan, particularly for late stage disease, may involve stem cell transplants into the photoreceptor or ganglion cell layers of the retina. Stem cells from young mouse retinas can be transplanted, and can form photoreceptors in adult retinas. These cells can be grown in tissue culture, but can no longer form photoreceptors. We have used microarrays to investigate differences in gene expression between cultured retinal progenitor cells (RPCs) that have lost photoreceptor potential, postnatal day 1 (pn1) retinas and the postnatal day 5 (pn5) retinas that contain transplantable photoreceptors. We have also compared FACS sorted Rho-eGFP expressing rod photoreceptors from pn5 retinas with Rho-eGFP negative cells from the same retinas. We have identified over 300 genes upregulated in rod photoreceptor development in multiple comparisons, 37 of which have been previously identified as causative of retinal disease when mutated. It is anticipated that this research should bring us closer to growing photoreceptors in culture and therefore better treatments for RD. This dataset is also a resource for those seeking to identify novel retinopathy genes in RD patients.
Gene expression changes during retinal development and rod specification.
No sample metadata fields
View SamplesGene expression profiling has demonstrated clinical utility as a predictive tool in clinical oncology. We have identified genes associated with invasion of pancreatic cancer, and with potential for identifying early recurrence.
No associated publication
Cell line
View Samplesmature female gametophyte (Arabidopsis thaliana) transcriptional profiling (single cell types)
No associated publication
Specimen part, Subject
View SamplesThis study set out to identify global changes in gene expression in AGS gastric epithelial cells following 8 hours stimulation with 10 g/ml lipopolysaccharide (LPS) from the gastric pathogen H. pylori.
Tribbles 3: a novel regulator of TLR2-mediated signaling in response to Helicobacter pylori lipopolysaccharide.
Specimen part, Cell line
View SamplesThis study set out to identify global changes in gene expression in MKN45 gastric epithelial cells following 8 hours stimulation with 10 g/ml lipopolysaccharide (LPS) from the gastric pathogen H. pylori.
Tribbles 3: a novel regulator of TLR2-mediated signaling in response to Helicobacter pylori lipopolysaccharide.
Specimen part, Cell line
View SamplesSOX2 is an oncogene and a core pluripotency transcription factor. SOX2 has multiple roles in various malignancies, in the maintainance of pluripotency and during various stages of embryonic development. Human embryonal carcinoma cells express SOX2 and the loss of this results in their differentiation.
An integrated analysis of the SOX2 microRNA response program in human pluripotent and nullipotent stem cell lines.
Specimen part, Cell line, Treatment
View SamplesWild-type and mouse mutants for FGF3, FGF10 and FGF3/FGF10 double mutants at embryonic day E10 were analysed by microarrays for downregulated genes. A tissue sample corresponding to an area containing the otic vesicle and surrounding mesenchyme and neighboring hindbrain were isolated from E10 embryos (See Figure 3A of manuscript). Five samples were pooled for RNA preparation. Samples were isolated from wild-type, FGF3, FGF10 and FGF3/FGF10 double mutants. Two RNA samples for each genotype were generated (corresponding to 8 tissue samples). RNA was labeled and hybridized with Affymetrix U74A V2 arrays.
FGF signalling controls expression of vomeronasal receptors during embryogenesis.
Age, Specimen part, Disease, Disease stage
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