Filters
Technology
Platform
GSE68256
Homo sapiens
50 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
HER2 is a tyrosine kinase receptor causally involved in cancer. A subgroup of breast cancer patients with particularly poor clinical outcome expresses a heterogeneous collection of HER2 carboxy-terminal fragments (CTFs). However, since the CTFs lack the extracellular domain that drives dimerization and subsequent activation of full-length HER2, they are in principle expected to be inactive. Here we present evidence that at low expression levels one of these fragments, 611-CTF, activated multiple signaling pathways because of its unanticipated ability to constitutively homodimerize. A transcriptomic analysis revealed that 611-CTF specifically controlled the expression of genes that we found correlated with poor prognosis in breast cancer. Among the 611-CTF-regulated genes were several that previously have been linked to metastasis, including MET, EPHA2, MMP1, IL11, ANGPTL4 and different Integrins. Transgenic mice overexpressing HER2 in the mammary gland develop tumors only after acquisition of activating mutations in the transgene. In contrast, we show that expression of 611-CTF led to development of aggressive and invasive mammary tumors without the need for mutations. These results demonstrate that 611-CTF is a potent oncogene capable of promoting mammary tumor progression and metastasis.
Publication Title
A naturally occurring HER2 carboxy-terminal fragment promotes mammary tumor growth and metastasis.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
The bacterial product lipopolysaccharide (LPS) stimulates nuclear factor kB (NF-kB) signaling, which results in the production of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), as part of the immune response. NF-kB target genes also include those encoding proteins that inhibit NF-kB signaling through negative feedback loops. By simultaneously studying the dynamics of the nuclear translocation of the NF-kB subunit RelA and the activity of a Tnf-driven reporter in a mouse macrophage cell line, Sung et al. found that the gene encoding RelA was also a target of NF-kB. Synthesis of RelA occurred only at higher concentrations of LPS and constituted a positive feedback loop that dominated over existing negative feedback mechanisms. Genes expressed in response to a high concentration of LPS were enriched for those involved in innate immune responses. Together, these data suggest that the RelA-dependent positive feedback loop enables macrophages to mount an effective immune only above a critical concentration of LPS.
Publication Title
Switching of the relative dominance between feedback mechanisms in lipopolysaccharide-induced NF-κB signaling.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We performed gene expression profiling of oligooxopiperazines (OPs) targeting the hypoxia-inducible transcription factor complex. Treatment of cells with OPs inhibited hypoxia-inducible gene expression in A549 cells.
Publication Title
In vivo modulation of hypoxia-inducible signaling by topographical helix mimetics.
Sample Metadata Fields
Cell line
View Samples- Schizosaccharomyces pombe
- 6 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
We show that the sensitivity of tsc mutant cells to rapamycin is mediated by TORC1 and can be suppressed by overexpression of the 2-oxoglutarate-Fe(II) dependent oxygenase, Isp7. We show that Isp7 is a novel regulator of amino acids uptake that acts via regulation of gene expression, both upstream and downstream of TOR signaling. suppressed by overexpression of the putative 2-oxoglutarate-Fe(II) dependent oxygenase, Isp7. We show that Isp7 is a novel master regulator of amino acids uptake that acts via regulation of gene expression, both upstream and downstream of TOR signaling.
Publication Title
Isp7 is a novel regulator of amino acid uptake in the TOR signaling pathway.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
Illumina HiSeq 2500
Description
We report a transcriptome comparison of HEK293 cells modified at the DPYSL2 gene promoter dinucleotide repeat (chr8:26,435,510-26,435,534) by CRISPR/Cas9 to change from the common 11 repeats to the more rare 13 repeats Overall design: 11/11 repeat HEK 293 cells were modified by CRISPR/Cas 9. Cell were flow sorted by the co-transfected GFP and single cells were expanded. From those we selected 4 modified and 8 unmodified clones for RNA seq. RNA was extracted at 80% confluency
Publication Title
The DPYSL2 gene connects mTOR and schizophrenia.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Microarray was used to identify differential gene expression pattern in Barrett's esophagus (BE), compared to the normal adjacent epithelia gastric cardia (GC) and normal squamous esophagus (NE)
Publication Title
Evidence for a functional role of epigenetically regulated midcluster HOXB genes in the development of Barrett esophagus.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We performed gene expression profiling of hydrogen-bond surrogate that targets hypoxia-inducible transcription factior complex and results in inhibition of hypoxia-inducible genes with relatively minimal perturbation of non-targeted signaling pathways.
Publication Title
Protein domain mimetics as in vivo modulators of hypoxia-inducible factor signaling.
Sample Metadata Fields
Cell line, Treatment
View Samples- Saccharomyces cerevisiae
- 9 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
To study how the presence of PUFAs influences central cellular processes, and in order to perform lipidome, transcriptome and molecular studies we decided to use yeast as a model organism. We therefore co-expressed 12-desaturase and 6- desaturase genes from Mucor rouxii in S. cerevisiae with the objective to obtain a yeast strain that contains PUFAs, especially linoleic acid (LA, C18:29,12) and -linolenic acid (GLA, C18:36,9,12), in its membranes.
Publication Title
Heterologous production of polyunsaturated fatty acids in Saccharomyces cerevisiae causes a global transcriptional response resulting in reduced proteasomal activity and increased oxidative stress.
Sample Metadata Fields
Time
View Samples- Mus musculus
- 7 Downloadable Samples
- Illumina HiSeq 2500
Description
Tumor-associated macrophages (TAMs) have immunosuppressive capacity in mouse models of cancer. Here we show that the genetic deletion of the microRNA (miRNA)-processing enzyme DICER in TAMs broadly programs them to a CD11c+MRC1-/low M1-like immunostimulatory phenotype characterized by activated interferon-? (IFN-?)/STAT1/IRF signaling. M1-like TAM programming fostered the recruitment of cytotoxic T-cells (CTLs), including tumor-antigen-specific CTLs, inhibited tumor growth, and enhanced the efficacy of PD1 checkpoint blockade. Bioinformatics analysis of TAM transcriptomes identified a limited set of miRNAs putatively involved in TAM programming. Re-expression of Let-7 in Dicer-deficient TAMs was sufficient to partly rescue the M2-like (protumoral) TAM phenotype and abate tumor CTL infiltration. Targeted suppression of DICER activity in TAMs may, therefore, stimulate antitumor immunity and enhance the efficacy of cancer immunotherapy. Overall design: To explore the role of DICER in the development, activation and immunological functions of TAMs, we crossed homozygous LysM-Cre (Clausen et al., 1999) with Dicerlox/lox (Harfe et al., 2005) mice to obtain mice with myeloid-cell-specific Dicer1 gene deletion (LysM-Cre;Dicer–/–, referred to as D–/–). These mice were then backcrossed to LysM-Cre to obtain the control LysM-Cre; Dicer+/+ mice (referred to as D+/+). Both LysM-Cre and Dicerlox/lox mutations were always homozygous in our experiment. We then inoculated Lewis lung carcinoma (LLC) cells subcutaneously (s.c.) in D–/– and control D+/+ mice. Once the tumors were established, we isolated by fluorescence-activated cell sorting (FACS) tumor-associated macrophages (F4/80+ cells).
Publication Title
Suppression of microRNA activity amplifies IFN-γ-induced macrophage activation and promotes anti-tumour immunity.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The main cell of origin of the Sonic hedgehog (SHH) subgroup of medulloblastoma (MB) is granule cell precursors (GCPs), a SHH-dependent transient amplifying population in the developing cerebellum. SHH-MBs can be further subdivided based on molecular and clinical parameters, as well as location since SHH-MBs occur preferentially in the lateral cerebellum (hemispheres). Our analysis of adult patient data suggests that tumors with Smoothened (SMO) mutations form more specifically in the hemispheres than those with Patched 1 (PTCH1) mutations. Using sporadic mouse models of SHH-MB with the two mutations commonly seen in adult MB, constitutive activation of Smo (SmoM2) or loss-of-Ptch1, we found that regardless of timing of induction or type of mutation, tumors developed primarily in the hemispheres with SmoM2-mutants indeed showing a stronger specificity. We further uncovered that GCPs in the hemispheres are more susceptible to high level SHH signaling compared to GCPs in the medial cerebellum (vermis), as more SmoM2 or Ptch1-mutant hemisphere cells remain undifferentiated and show increased tumorigenicity when transplanted. Finally, we identified location-specific GCP gene expression profiles, and found that deletion of the genes most highly expressed in the hemispheres (Nr2f2) or vermis (Engrailed1) showed opposing effects on GCP differentiation. Our studies thus provide new insights into intrinsic differences within GCPs that impact on SHH-MB progression.
Publication Title
Lateral cerebellum is preferentially sensitive to high sonic hedgehog signaling and medulloblastoma formation.
Sample Metadata Fields
Specimen part
View Samples