To assess the global effects of HOXC11 in endocrine resistant breast cancer cells we performed RNA-seq on LY2 cells which were transfected with either siRNA targeting HOXC11 (siHOXC11) or a scrambled negative control siRNA (scrHOXC11) in the presence of 4-OH-tamoxifen (10-8M). Knockdown was verified by Taq-man qRT-PCR prior to library preparation. RNA (10µg) was extracted using an Oligotex mRNA kit (Qiagen) as per manufacturer’s instructions (n=4). RNA was reverse transcribed followed by mRNA library preparation and sequencing based on a protocol outlined by Wilhelm et al., 2010. Sequencing was performed on an Illumina Genome Analyzer II (GAII) (54 million reads per sample on average). Overall design: Silencing of HOXC11 in tamoxifen resistant LY2 cells to identify putative HOXC11 target genes.
Prosaposin activates the androgen receptor and potentiates resistance to endocrine treatment in breast cancer.
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View SamplesThe development of breast cancer resistance to endocrine therapy results from an increase in cellular plasticity leading to the development of a steroid independent tumour. The p160 steroid coactivator protein SRC-1, through interactions with developmental proteins and other non-steroidal transcription factors drives this tumour adaptability. Here, using discovery studies we identify ADAM22, a non-protease member of the ADAMs family, as a direct target of SRC-1, independent of estrogen receptor(ER). Molecular, cellular, in vivo and clinical studies confirmed SRC-1 as a regulator of ADAM22 and established a role for ADAM22 in endocrine resistant tumour progression. ADAM22 has the potential to act as a therapeutic drug target and a companion predictive biomarker in the treatment of endocrine resistant breast cancer.
Global characterization of the SRC-1 transcriptome identifies ADAM22 as an ER-independent mediator of endocrine-resistant breast cancer.
Cell line, Treatment
View SamplesSplenocytes from lymphoreplete, unmanipulated mice were analyzed for basal mRNA levels. We hypothesized, based on previous data from our lab and others, that many cytokine/inflammatory response genes would show an increase from na誰ve CD5lo<CD5hi<Virtual memory. Overall design: mRNA was analyzed from mouse splenocytes separated into na誰ve CD5lo, na誰ve CD5hi, and virtual memory cells. Mice were lymphoreplete and unmanipulated.
Virtual memory T cells develop and mediate bystander protective immunity in an IL-15-dependent manner.
Cell line, Subject
View SamplesIn order to define the targets of two miRNA overexpressed in NK cells in CFS/ME paitents, miRNA precursors for hsa-miR-99b and hsa-miR-330-3p were transfected in to buffy coat derived Natural Killer cells isolated by negative magnetic selection.
MicroRNAs hsa-miR-99b, hsa-miR-330, hsa-miR-126 and hsa-miR-30c: Potential Diagnostic Biomarkers in Natural Killer (NK) Cells of Patients with Chronic Fatigue Syndrome (CFS)/ Myalgic Encephalomyelitis (ME).
Specimen part, Disease, Disease stage
View SamplesWe profiled primary breast cancer, nodal and liver metastatic tumours from three patients. At the time of initial diagnosis, all three patients presented with luminal breast cancer with adjacent nodal metastasis. They all received 5 years of enodrine therapy and all subsequently developed liver metastasis. Overall design: Examination of mRNA differences between primary, nodal and metastatic tumour samples.
Transcriptomic Profiling of Sequential Tumors from Breast Cancer Patients Provides a Global View of Metastatic Expression Changes Following Endocrine Therapy.
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View SamplesMicroglia are fundamentally important immune cells within the central nervous system (CNS) that respond to environmental challenges to maintain normal physiological processes. Alterations in steady-state cellular function and over-activation of microglia can facilitate the initiation and progression of neuropathological conditions such as Alzheimer's disease, Multiple Sclerosis, and Major Depressive Disorder. Alcohol consumption disrupts signaling pathways including both innate and adaptive immune responses that are necessary for CNS homeostasis. Unbiased RNA-Seq profiling was used to identify gene expression changes in isolated microglia in response to recurring bouts of voluntary alcohol drinking behavior. Gene coexpression analysis identified a coordinately regulated group of genes, unique to microglia, that collectively are associated with alcohol consumption. Several genes in this group were involved in toll-like receptor signaling and production of the inflammatory cytokine interferon-gamma. Coordinate expression of these genes is not ascertained from an admixture of CNS cell-types, underscoring the importance of examining isolated cellular populations to reveal systematic gene expression changes arising from mature microglia. We identified a distinctive microglial gene expression signature for neuroimmune responses related to alcohol consumption that provides valuable insight into microglia-specific changes underlying the development of substance abuse, as well as related CNS disorders. Overall design: We examined mRNA from both total homogenate (mixture of all cell types) and microglia from the cortex of control mice and mice that have undergone chronic voluntary ethanol consumption
Microglial-specific transcriptome changes following chronic alcohol consumption.
Specimen part, Cell line, Treatment, Subject
View SamplesGlobal gene expression patterns were determined from microarray results on day 1, 3, 5, 7, 10 and 14 during plantaris muscle hypertrophy induced by synergist ablation in young adult mice (5 months).
Time course of gene expression during mouse skeletal muscle hypertrophy.
Sex, Age, Specimen part, Treatment, Time
View SamplesPathogen-specific polyfunctional T cell responses have been associated with favorable clinical outcomes but it is not known whether polyfunctional T cells are distinct from monofunctional cytokine producing T cells. In this study we compared the transcriptomic profile of P. falciparum reactive polyfunctional and IFNg monofunctional CD4 T cells by microarray analysis and show that polyfunctional CD4 T cells are associated with a unique transcriptomic signature.
Polyfunctional and IFN-<b>γ</b> monofunctional human CD4<sup>+</sup> T cell populations are molecularly distinct.
No sample metadata fields
View SamplesTranscriptome analysis of skeletal muscle during hypertrophic growth in aged mice
Blunted hypertrophic response in aged skeletal muscle is associated with decreased ribosome biogenesis.
Sex, Age, Specimen part, Time
View SamplesThe Snf1 kinase plays a critical role in recalibrating cellular metabolism in response to glucose depletion. Hundreds of genes show changes in expression levels when the SNF1 gene is deleted. However, cells can adapt to the absence of a specific gene when grown in long term culture. Here we apply a chemical genetic method to rapidly and selectively inactivate a modified Snf1 kinase using a pyrazolopyrimidine inhibitor. By allowing cells to adjust to a change in carbon source prior to inhibition of the Snf1 kinase activity, we identified a set of genes whose expression increased when Snf1 was inhibited. Prominent in this set are genes that are activated by Gcn4, a transcriptional activator of amino acid biosynthetic genes. Deletion of Snf1 increased Gcn4 protein levels without affecting its mRNA levels. The increased Gcn4 protein levels required the Gcn2 kinase and Gcn20, regulators of GCN4 translation. These data indicate that Snf1 functions upstream of Gcn20 to regulate control of GCN4 translation.
A chemical genomics study identifies Snf1 as a repressor of GCN4 translation.
No sample metadata fields
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