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Transcription profiling of mouse B lymphocytes after thapsigargin-stimulated ER stress for 8 and 24 hours to elucidate factors that influence T cell priming

ABSTRACT: Time course data from thapsigargin-stimulated ER stress for 8 and 24 hours, in order to elucidate factors that influence T cell priming.

ORGANISM(S): Mus musculus

SUBMITTER: Ivan Wick

PROVIDER: E-TABM-240 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Transcription profiling of various cell types isolated from pancreatic islet grafts in Id1/Id3 deficient and wild type mice

Project description:To gain insights into the genetic program activated within the distinct vascular and inflammatory transplant microenvironments in Id1/Id3 deficient and WT mice, we performed a series of gene screening experiments using RNA from total graft tissue as well as from myeloid and endothelial (i.e., CD31+ and ISB4+) cells isolated from the grafts at 1 week post-transplantation.

2008-06-13 | E-TABM-355 | biostudies-arrayexpress

Characterising the cellular activity of new Fibroblast Growth Factor Receptor tyrosine kinase inhibitors and identification of a gatekeeper mutation in FGFR3 as a mechanism of acquired resistance.

Project description:Fibroblast growth factor receptors (FGFRs) can act as driving oncoproteins in certain cancers due to mutation, over-expression or activating gene fusions and are therefore attractive drug targets. Here we have characterized tumour cell responses to three new inhibitors of FGFR1-3, AZ12576089, AZ12908010 and the clinical candidate AZD4547, making comparisons with the well-characterized FGFR inhibitor PD173074. Using a panel of 16 human tumour cell lines we show that the anti-proliferative activity of AZ12908010 and AZD4547 is strongly linked to the presence of de-regulated FGFR signalling. In contrast, AZ12576089 was also able to inhibit proliferation of cells lacking de-regulated FGFR, suggesting off-target effects. Acquired resistance to targeted tyrosine kinase inhibitors (TKIs) is a growing problem in the clinic. To assess how FGFR-dependent tumour cells may adapt to long-term exposure to FGFR inhibitors we generated a derivative of the KMS-11 myeloma cell line (FGFRY373C) with acquired resistance to AZ12908010 (KMS-11R cells). Basal P-FGFR3, P-FRS2 and P-ERK1/2 and D-type cyclins were all inhibited by AZ12908010 in parental KMS-11 cells whereas these markers were constitutively elevated and refractory to drug in KMS-11R cells. Sequencing of FGFR3 in KMS-11R cells revealed the presence of a heterozygous mutation at the gatekeeper residue, encoding FGFR3V555M. Consistent with this KMS-11R cells were cross-resistant to AZD4547 and PD173074 but remained fully sensitive to AZ12576089, confirming that the anti-proliferative effects of AZ12576089 are not related to FGFR inhibition. These results define the selectivity and efficacy of two new FGFR inhibitors and identify a secondary gatekeeper mutation as a mechanism of acquired resistance to FGFR inhibitors that should be anticipated as clinical evaluation proceeds.

2012-10-02 | E-TABM-1222 | biostudies-arrayexpress

Transcription profiling of human 239T cells shows SUMOylation of DRIL1 directs its transcriptional activity towards leukocyte lineage-specific genes

Project description:SUMOylation of DRIL1 directs its transcriptional activity towards leukocyte lineage-specific genes

2009-06-26 | E-TABM-681 | biostudies-arrayexpress

Transcription profiling of human fibroblast cells from punch skin biopsies obtained from 2 MACS syndrome patients and 4 ethnically matched healthy controls.

Project description:We found a candidate region (with 55 known or predicted genes) that was found to linkage to the MACS syndrome. Because it is transmitted in an autosomal recessive fashion, and given the fact most recessive disorders are caused by loss-of-function mutations often resulting in decreased mRNA levels, we hypothesized that screening the expression of the various genes located within the disease interval may point to candidate genes of interest. We therefore established fibroblast cell lines from punch skin biopsies obtained from 2 patients and 4 ethnically matched healthy controls. We then compared global gene expression using microarrays in the 6 cell lines (all genes contained within the disease interval were represented on the array).

2009-08-01 | E-TABM-735 | biostudies-arrayexpress

Transcription profiling by array of human untreated endometrial cancer cell lines

Project description:Gene expression array analysis of 8 untreated endometrial cancer cell lines using Illumina human WG6 version 2

2010-09-25 | E-TABM-992 | biostudies-arrayexpress

Transcription profiling of human KNS42 cells treated with the dual pI3-kinas/mTOR inhibitor PI-103

Project description:Sensitivity to temozolomide (TMZ) is restricted to a subset of glioblastoma patients, with the major determinant of resistance a lack of promoter methylation of the gene encoding the DNA methyltransferase MGMT, although other mechanisms are thought to be active. In a genome-wide screen of paediatric and adult glioma cells, we identified a co-ordinated upregulation of HOX gene expression in the MGMT-independent cell line KNS42. As a recent study has proposed a mechanism for this observation whereby transcriptional activation of the HOXA cluster is reversible by a PI3-kinase inhibitor through an epigenetic mechanism involving histone H3K27 trimethylation, we sought to investigate whether this was active in our system. We thus treated KNS42 cells for 24 hours with the dual PI3-kinase / mTOR inhibitor PI-103 at 5x IC50 and carried out gene expression profiling using Illumina HT-12 microarrays.

2011-01-08 | E-TABM-890 | biostudies-arrayexpress

ChIP-chip by array of human mesenchymal stem cells to identify Argonaute1 bound mRNAs and to identify mRNAs expressed by the human embryo stem cell line H1 before and after differentiation along the neural lineage.

Project description:Gene expression profiles were generated with Illumina arrays for untreated human mesenchymal stem cells and also Argonaute1 bound mRNAs in the same cells. In addition gene expression profiles were generated for the human embryo cell line H1 before and after differentiation along the neural lineage. NOTE: assays for human embryonic stem cells before and after differentiation were added in July 2014 and data files for the mesenchymal stem cells were updated.

2010-12-20 | E-TABM-1001 | biostudies-arrayexpress

The long non-coding HOTAIR is modulated by cyclic stretch and WNT/beta-CATENIN in human aortic valve cells and is a novel repressor of calcification genes

Project description:Aortic valve calcification is a significant and serious clinical problem for which there are no effective medical treatments. Individuals born with bicuspid aortic valves, 1-2% of the population, are at the highest risk of developing aortic valve calcification. Aortic valve calcification involves increased levels of calcification and inflammatory genes. Bicuspid aortic valve leaflets experience increased strain. The molecular mechanisms involved in the pathogenesis of calcification of BAVs are not well understood, especially the molecular response to mechanical stretch. HOTAIR is a long non-coding RNA (lncRNA) that has been implicated with cancer but has not been studied in cardiac disease. We have found that HOTAIR levels are decreased in BAVs and in human aortic interstitial cells (AVICs) exposed to cyclic stretch. Reducing HOTAIR levels via siRNA in AVICs results in increased expression of calcification genes.

2014-05-02 | E-MTAB-2409 | biostudies-arrayexpress

Methylation and microRNA profiling of human paediatric glioma cell lines

Project description:Constitutive signalling pathway activation is a key feature of primary tumours and cancer cell lines. The regulation of gene expression changes may be via both genomic and epigenetic means, and understanding the mechanisms by which signal transduction may be activated can provide rational targets for therapeutic intervention. We have previously carried out DNA copy and expression profiling on a unique panel of five paediatric glioma cell lines, and have noted only a limited influence of gene amplification on gene expression. In the present study we have extended our work to include a measure of global methylation changes as well as micro RNA profiling in the same cell lines. We noted various instances of signalling pathway activation associated with specific hypermethylation or miRNA regulation of gene expression at various effectors also observed in primary paediatric tumours. These data provide evidence for the multifaceted nature of gene expression changes in paediatric high grade glioma, and identify novel targets for targeted therapy in this treatment refractory disease.

2010-12-03 | E-TABM-858 | biostudies-arrayexpress

Transcription profiling of human paediatric glioblastoma cells treated with insulin-like growth factor 1 receptor inhibitors

Project description:We have previously determined the insulin-like growth factor 1 receptor (IGF1R) to be amplified and overexpressed in paediatric glioblastoma. In order to probe the efficacy and mechanisms of action of various inhibitors of the receptor, we have carried out expression profiling of paediatric glioblastoma cells treated with 5x IC50 of the compounds PPP and NVP-AEW541 over a 24 hour time-course.

2011-01-08 | E-TABM-889 | biostudies-arrayexpress

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