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GSE104397
Mus musculus
80 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Loss of E2F transcription factos alters metastatic capacity of MMTV-PyMT tumors.
Publication Title
Histological subtypes of mouse mammary tumors reveal conserved relationships to human cancers.
Sample Metadata Fields
Disease
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Monoclonal antibodies (mAbs) targeting the oncogenic receptor tyrosine kinase ERBB2/HER2, such as Trastuzumab, are the standard of care therapy for breast cancers driven by ERBB2 overexpression and activation. However, a substantial proportion of patients exhibits de novo resistance. Here, by comparing matched Trastuzumab-naïve and post-treatment patient samples from a neoadjuvant trial, we link resistance with elevation of H3K27me3, a repressive histone modification catalyzed by Polycomb Repressor Complex 2 (PRC2). In ErbB2+ breast cancer models, PRC2 silences endogenous retroviruses (ERVs) to suppress anti-tumor Type-I interferon (IFN) responses. In patients, elevated H3K27me3 in tumor cells following Trastuzumab treatment correlates with suppression of IFN-driven viral defense gene expression signatures and poor response. Using an immunocompetent model, we provide evidence that EZH2 inhibitors promote IFN-driven immune responses that enhance the efficacy of anti-ErbB2 mAbs, suggesting the potential clinical benefit of epigenomic reprogramming by H3K27me3 depletion in Trastuzumab-resistant disease.
Publication Title
Reduction of Global H3K27me<sup>3</sup> Enhances HER2/ErbB2 Targeted Therapy.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 47 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Myc oncogenic signature in Papillary type 2b
Publication Title
Detection of DNA copy number changes and oncogenic signaling abnormalities from gene expression data reveals MYC activation in high-grade papillary renal cell carcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 116 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Thyroid gland is among the most sensitive organs to ionizing radiation. Whether low-dose radiation-induced papillary thyroid cancer (PTC) differs from sporadic PTC is yet unknown.
Publication Title
Gene signature of the post-Chernobyl papillary thyroid cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 9 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Skeletal muscle senescence influences whole organism aging, yet little is known on the relay of pro-longevity signals from muscles to other tissues. We performed an RNAi screen in Drosophila for muscle-released cytokines (?myokines?) regulating lifespan and identified Myoglianin, the homolog of human Myostatin. Myoglianin is induced in skeletal muscles by the transcription factor Mnt and together they constitute an inter-organ signaling module that regulates lifespan, age-related muscle dysfunction, and protein synthesis across aging tissues. Both Mnt and Myoglianin activate already in young age the protective decline in protein synthesis that is typical of old age, while knock-down of Myoglianin impairs this process. Mechanistically, Mnt decreases the expression of nucleolar components in muscles while also decreasing nucleolar size in distant tissues via Myostatin/p38 MAPK signaling. Our results highlight a myokine-dependent inter-organ longevity pathway that coordinates nucleolar function and protein synthesis across aging tissues.
Publication Title
Intertissue control of the nucleolus via a myokine-dependent longevity pathway.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
E-cadherin downregulation in cancer cells is associated with epithelial-to-mesenchymal transition (EMT) and metastatic prowess, but the underlying mechanisms are incompletely characterized. In this study, we probed E-cadherin expression at the plasma membrane as a functional assay to identify genes involved in E-cadherin downregulation. The assay was based on the E-cadherin-dependent invasion properties of the intracellular pathogen Listeria monocytogenes. On the basis of a functional readout, automated microscopy and computer-assisted image analysis were used to screen siRNAs targeting 7,000 human genes. The validity of the screen was supported by its definion of several known regulators of E-cadherin expression, including ZEB1, HDAC1 and MMP14. We identified three new regulators (FLASH, CASP7 and PCGF1), the silencing of which was sufficient to restore high levels of E-cadherin transcription. Additionally, we identified two new regulators (FBXL5 and CAV2), the silencing of which
Publication Title
Novel strategies to enforce an epithelial phenotype in mesenchymal cells.
Sample Metadata Fields
Age, Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The beta1-adrenergic receptor (beta1AR; ADRB1) polymorphism Arg 389Gly is located in an intracellular loop and is associated with distinct human and mouse cardiovascular phenotypes. To test the hypothesis that beta1-Arg389 and beta1-Gly389 alleles could differentially couple to pathways beyond that of classic Gs-adenylyl cyclase (AC)/cAMP signaling, we performed comparative gene expression profile analyses on hearts from wildtype and transgenic mice that expressed either human beta1-Arg389 and beta1-Gly389 receptors, or AC5 adenyl cyclase, sampling at an early age and stage, prior to the onset of pathologic features. We observed substantial overlap of dysregulated genes across all three transgenic heart models, consistent with a shared coupling to cAMP-dependent regulation of cardiac processes and adaptive responses. All three models up-regulated genes associated with RNA metabolism and translation, and down-regulated genes associated with mitochondria and energy metabolism, consistent with cAMP-driven increase in cardiac contractility, protein synthesis, and compensatory down-regulation of mitochondrial energy production. Both beta1AR transgenics activated additional genes associated with kinase-dependent pathways, and uniquely, beta1-Arg389 hearts caused up-regulation of genes associated with inflammation, programmed cell death, and extracellular matrix. These results substantially expand the scope of 7-transmembrane domain receptor signaling propagation beyond known cognate G-protein couplings. Moreover, they implicate alterations of a repertoire of processes evoked by a single amino acid variation in the cardiac beta1AR that might be exploited for genotype-specific heart failure diagnostics and therapeutics.
Publication Title
Differential coupling of Arg- and Gly389 polymorphic forms of the beta1-adrenergic receptor leads to pathogenic cardiac gene regulatory programs.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
Escherichia coli release Extracellular Vesicles (EVs) which carry diverse molecular cargo. Pathogenic E.coli EVs contain virulence factors which assist during infection in the host in different mechanisms.The RNA cargo of E.coli EVs has not been assessed in their effect in the host. We used microarray data to asses and compare the global response of bladder cells to EV-RNA from pathogenic E.coli (Uropathogenic UPEC 536) and non-pathogenic E. coli (probiotic Nissle 1917)
Publication Title
Effect of the Extracellular Vesicle RNA Cargo From Uropathogenic <i>Escherichia coli</i> on Bladder Cells.
Sample Metadata Fields
Disease
View Samples- Mus musculus
- 18 Downloadable Samples
Illumina HiSeq 2000
Description
Analysis of the coordinated transcriptional reponse to heat shock and ER stress Overall design: mRNA profiles of NIH3T3 cells which stably expressing DD-sfGFP were generated by deep sequencing, in triplicate, using Illumina HiSeq. The samples were collected from indicated timepoints after exposed to either heat stress or ER stress.
Publication Title
Distinct transcriptional responses elicited by unfolded nuclear or cytoplasmic protein in mammalian cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Illumina HiSeq 2000
Description
Analysis of the coordinated transcriptional response to unfolded proteins in cytosol and nucleus utilizing mRNA-seq Overall design: mRNA profiles of NIH3T3 cells which stably expressing DD-sfGFP were generated by deep sequencing using Illumina HiSeq2000. The samples were collected from indicated timepoints after Shield-1 removal.
Publication Title
Distinct transcriptional responses elicited by unfolded nuclear or cytoplasmic protein in mammalian cells.
Sample Metadata Fields
No sample metadata fields
View Samples