Removal of the transcription factor SAP1a member of the Ternary Complex Factor (TCF) group of transcription factors which in conjunction with Serum Response Factor (SRF) has been shown to have a profound effect on positive selection in the thymus. When another TCF Elk1 is knocked out in mice there is no effect on positive selection unless it is on a Sap1a KO background where the phenotype is very severe. We have stimulated isolated double positive T cells (DPs) with anti-CD3 to mimic positive selection and compared basal and stimulated transcription across the four genotypes to discover the downstream targets of Sap1a involved in positive selection.
Ternary complex factors SAP-1 and Elk-1, but not net, are functionally equivalent in thymocyte development.
Sex, Age, Specimen part, Treatment
View SamplesWe sought to examine the mechanism through which phospho-mutants can contribute to the transformation of MCF10A acini. To investigate this, we examined the RNA abundance of Myc and Myc phospho-mutants (T58A, S71A/S81A, and Myc-4A) against a GFP control.
MYC phosphorylation at novel regulatory regions suppresses transforming activity.
Cell line
View SamplesGene expression analysis of a unique HNSCC (Head and Neck Squamous Cell Carcinoma) localization, the hypopharynx. Four normal and 34 tumor samples were analysed using Affymetrix HG-U95A microarrays containing probe sets representing ~12650 distinct transcription features.
Identification of genes associated with tumorigenesis and metastatic potential of hypopharyngeal cancer by microarray analysis.
No sample metadata fields
View SamplesCHEK2 1100delC is a moderate-risk cancer susceptibility allele that confers a high breast cancer risk in a polygenic setting. Gene expression profiling of CHEK2 1100delC breast cancers may reveal clues to the nature of the polygenic CHEK2 model and its genes involved. Here, we report global gene expression profiles of a cohort of 155 familial breast cancers, including 26 CHEK2 1100delC mutant tumors. A 40-gene CHEK2 signature was defined that significantly associated with CHEK2 1100delC breast cancers. The identification of a CHEK2 gene signature implies an unexpected biological homogeneity among the CHEK2 1100delC breast cancers. In addition, all 26 CHEK2 1100delC tumors classified as luminal intrinsic subtype breast cancers, with 8 luminal A and 18 luminal B tumors. This biological make-up of CHEK2 1100delC breast cancers suggests that a relatively limited number of additional susceptibility alleles are involved in the polygenic CHEK2 model. Identification of these as-yet-unknown susceptibility alleles should be aided by clues from the 40-gene CHEK2 signature.
Gene expression profiling assigns CHEK2 1100delC breast cancers to the luminal intrinsic subtypes.
Specimen part
View SamplesThis study aims at identifying genes that are NIK/NF-kappaB2 responsive in murine dendritic cells matured in vivo.
Dendritic cells require the NF-kappaB2 pathway for cross-presentation of soluble antigens.
No sample metadata fields
View SamplesIn germ cells, Piwi proteins interact with a specific class of small non-coding RNAs, piwi-interacting RNAs (piRNAs). Together, these form a pathway that represses transposable elements, thus safeguarding germ cell genomes. While basic models describe the operation of piRNA pathways, neither the protein compositions of Piwi complexes, the critical protein-protein interactions that drive small RNA production and target recognition, or the precise molecular consequences of conserved localization to germline structures, call nuage, is well understood. We purified the three murine Piwi family proteins, Mili, Miwi, and Miwi2, from mouse germ cells and characterized their interacting protein partners. Piwi proteins were found in complex with Prmt5/Wdr77, an enzyme that di-methylates arginine residues. By immunoprecipitation with specific antibodies and by mass spectrometry, we found that Piwi proteins are arginine methylated at conserved positions in their amino termini. These modifications are essential to direct complex formation with specific Tudor-domain proteins, whose interactions with Piwis can be required for localization of RNP complexes in cytoplasmic nuage, proper piRNA expression, and transposon silencing. Considered together, our findings indicate that arginine methylation drives the assembly of multi-protein machines whose integrity and specific sub-cellular localization is necessary for efficient function of the piRNA pathway. Keywords: gene regulation study Overall design: Total small RNA in embryonic and post-birth mouse testes of tdrd1 and tdrd6 mutants
RNF17 blocks promiscuous activity of PIWI proteins in mouse testes.
No sample metadata fields
View SamplesThalidomide Exerts Distinct Molecular Antileukemic Effects and Combined Thalidomide/Fludarabine Therapy is Clinically Effective in High-Risk Chronic Lymphocytic Leukemia
Thalidomide exerts distinct molecular antileukemic effects and combined thalidomide/fludarabine therapy is clinically effective in high-risk chronic lymphocytic leukemia.
No sample metadata fields
View SamplesThe genes regulated by SOX11 in MCL was investigated in MCL cell line Granta 519 by siRNA knock down system. Cells were transfected using the LONZA electroporation system. Results represent cells harvested after 20 hours. Details of the experiment is published in PMID 21124928.
Gene expression profiling and chromatin immunoprecipitation identify DBN1, SETMAR and HIG2 as direct targets of SOX11 in mantle cell lymphoma.
Specimen part, Cell line
View SamplesGlucocorticoids (GC) have a major impact on the biology of normal and malignant cells of the lymphoid lineage. This includes induction of apoptosis which is exploited in the therapy of acute lymphoblastic leukemia (ALL) and related lymphoid malignancies. MicroRNAs (miRNAs) and the related mirtrons are ~22 nucleotide RNA molecules implicated in the control of essential biological functions including proliferation, differentiation and apoptosis. They derive from polymerase-II transcripts but whether GCs regulate miRNA-encoding transcription units is not known. We investigated miRNA/mirtron expression and GC regulation in 8 ALL in vitro models and 13 ALL children undergoing systemic GC monotherapy using a combination of expression profiling techniques, real time RT-PCR and northern blotting to detect mature miRNAs and/or their precursors. We identified a number of GC-regulated miRNAs/mirtrons, including the myeloid-specific miR-223 and the apoptosis and cell cycle arrest-inducing mir15~16 cluster. Thus, the observed complex changes in miRNA/mirtron expression during GC treatment might contribute to the anti-leukemic GC effects in a cell context dependent manner.
Glucocorticoid-regulated microRNAs and mirtrons in acute lymphoblastic leukemia.
No sample metadata fields
View SamplesIn this study we compared the effects of IL-2, IL-15, and IL-21 on the gene expression, activation of cell signaling pathways, and functional properties of cells derived from the CD4+ cutaneous T-cell lymphoma (CTCL). Whereas both IL-2 and IL-15 that signal through receptors that share the common gamma chain and the beta chain modulated the expression of >1,000 genes, IL-21 that signals via the receptor also containing gamma chain up-regulated <40 genes. All three cytokines induced tyrosine phosphorylation of Jak1 and Jak3. However, only IL-2 and IL-15 strongly activated STAT5, PI3K/Akt, and MEK/ERK signaling pathways. In contrast, IL-21 selectively activated STAT3. Whereas all three cytokines protected CTCL cells from apoptosis, only IL-2 and IL-15 promoted their proliferation. The effects of the cytokine stimulation were Jak3- and Jak1-kinase dependent. These findings document the vastly different impact of IL-2 and IL-15 vs. IL-21 on malignant CD4+ T cells. They also suggest two novel therapeutic approaches to CTCL and, possibly, other CD4+ T cell lymphomas: inhibition of the Jak1/Jak3 kinase complex and, given the known strong immunostimulatory properties of IL-21 on CD8+ T, NK, and B cells, application of this cytokine to boost an immune response against malignant CD4+ T cells.
Differential effects of interleukin-2 and interleukin-15 versus interleukin-21 on CD4+ cutaneous T-cell lymphoma cells.
No sample metadata fields
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