IKB Kinase beta (IKKB), a key component of the NFKB signalling pathway plays an important role in inflammation and cancer. Here we describe a previously unknown role of the IKK/FoxO3a axis in bone metastasis. We found that IKK was highly expressed in invasive human breast tumours and that levels of expression were elevated in bone metastasis. Overexpression of IKK in parental and bone-tropic human breast cancer cell-lines increased tumour volume, worsened cachexia, promoted osteolysis and increased mortality in adult mice whereas pharmacological inhibition and knockdown of IKK were inhibitory. Inhibition of IKK in breast cancer cell lines and bone cells stimulated bone formation and reduced tumour growth by a mechanism that was mediated in part, by cytoplasmic sequestering of FoxO3a independently of NFKB inhibition. We conclude that IK contributes significantly to the regulation of tumour growth and osteolysis in breast cancer by NFKB dependent and independent mechanisms.
Regulation of breast cancer induced bone disease by cancer-specific IKKβ.
Cell line
View SamplesIn this experiment we profiled the transcriptome of intestinal colonic epithelium and total colonic tissue of animals colonized with T.mu versus naïve littermate controls at different time points Overall design: Groups of three mice were inoculated with 2x106 highly purified Tritrichomonas musculis. Total tissue and epithelial cells were collected at 3 days, 14 days and 48 days after inoculation from three different mice. RNA was isolated and sequenced
Host-Protozoan Interactions Protect from Mucosal Infections through Activation of the Inflammasome.
Specimen part, Subject
View SamplesGenomewide analysis of gene expression associated with Tcof1 in mouse neuroblastoma. NB N1E-115 cells with wildtype, overexpression, knockdown of Tcof1.
Genomewide analysis of gene expression associated with Tcof1 in mouse neuroblastoma.
No sample metadata fields
View SamplesPericytes are integral components of the tissue vasculature and have essential functions in tumour angiogenesis. Endosialin (CD248) is a type I transmembrane glycoprotein highly expressed on pericytes in the tumour vasculature of most solid tumours, however it is low or negligibly expressed on normal tissue pericytes. Experiments using wild-type and endosialin-knockout mice has revealed that stromal endosialin expression facilitates intravasation of tumor cells from the primary tumor into the circulation, thereby promoting metastatic dissemination.
Endosialin-Expressing Pericytes Promote Metastatic Dissemination.
Sex, Specimen part, Disease
View SamplesSynapTRAP. Identification of Synaptic mRNA of neurons of the cortex. Technique combines sucrose percoll fractionation of a synaptically rich sample (SN) and TRAP tagged ribosome IP (PreIP and PostIP). This experiment uses pan neuronal SNAP25 mice and a cortical dissection. Overall design: Three replicates of four samples.
Transcriptomic Analysis of Ribosome-Bound mRNA in Cortical Neurites <i>In Vivo</i>.
Specimen part, Subject
View SamplesReconstitution of cytomegalovirus (CMV)-specific immunity following transplant remains a primary clinical objective to prevent CMV disease, and adoptive immunotherapy of CMV-specific T cells can be an effective therapeutic approach. Due to the persistence of CMV, most CMV-specific CD8+ T cells become terminally differentiated effector cells (TEFF). However, a minor subset retains a memory phenotype (TM). Interestingly, recent studies suggest that CMV-specific CD8+ T cells with different phenotypes may have different abilities to reconstitute sustained immunity following transfer. The immunology of human CMV (HCMV) infections is reflected in the mouse model of MCMV infection. We found that HCMV- and MCMV-specific T cells displayed shared genetic programs, validating the MCMV model for studies of CMV-specific T cells in vivo. After transfer, the proliferative capacity of MCMV-specific TM cells was vastly superior to TEFF cells. Strikingly, TM cells expanded and established sustained and diverse T cell populations even after multiple challenges. Although both TEFF and TM cells could protect Rag-/- mice, only TM cells could consistently survive after transfer into immune replete, latently infected recipients and respond if recipient immunity was lost. These data show that CMV-specific TM cells retain memory function during persistent infection and can re-establish CMV immunity when necessary.
Memory T cells specific for murine cytomegalovirus re-emerge after multiple challenges and recapitulate immunity in various adoptive transfer scenarios.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Dynamic changes in 5-hydroxymethylation signatures underpin early and late events in drug exposed liver.
Sex, Specimen part, Treatment, Time
View SamplesDynamic changes in the mouse liver DNA methylome associated with short (1 day) and prolonged (7, 28 and 91 days) exposure to the rodent liver non-genotoxic carcinogen (NGC), phenobarbital (PB).
Dynamic changes in 5-hydroxymethylation signatures underpin early and late events in drug exposed liver.
Specimen part, Treatment
View SamplesHyperglycemia is an essential factor leading to micro- and macrovascular diabetic complications. Macrophages are key innate immune regulators of inflammation that undergo 2 major directions of functional polarization: classically (M1) and alternatively (M2) activated macrophages. The aim of the study was to examine the effect of hyperglycemia on transcriptional activation of M0, M1 and M2 human macrophages.
Hyperglycemia induces mixed M1/M2 cytokine profile in primary human monocyte-derived macrophages.
Specimen part, Treatment, Subject
View Samples29-32 days old male mice where either treated with Phenobarbital or untreated
Dynamic changes in 5-hydroxymethylation signatures underpin early and late events in drug exposed liver.
Sex, Specimen part, Treatment, Time
View Samples