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GSE56704
Mus musculus
44 Downloadable Samples
Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Densely ionizing radiation is a major component of the space radiation environment and has potentially greater carcinogenic effect compared to sparsely ionizing radiation that is prevalent in the terrestrial environment. It is unknown to what extent the irradiated microenvironment contributes to the differential carcinogenic potential of densely ionizing radiation. To address this gap, 10-week old BALB/c mice were irradiated with 100 cGy sparsely ionizing g-radiation or 10, 30, or 80 cGy of densely ionizing, 350 MeV/amu Si particles and transplanted 3 days later with syngeneic Trp53 null mammary fragments. Tumor appearance was monitored for 600 days. Tumors arising in Si-particle irradiated mice had a shorter median time to appearance, grew faster and were more likely to metastasize. Most tumors arising in sham-irradiated mice were ER-positive, pseudo-glandular and contained both basal keratin 14 and luminal keratin 8/18 cells (designated K14/18), while most tumors arising in irradiated hosts were K8/18 positive (designated K18) and ER negative. Comparison of K18 vs K14/18 tumor expression profiles showed that genes increased in K18 tumors were associated with ERBB2 and KRAS while decreased genes overlapped with those down regulated in metastasis and by loss of E-cadherin. Consistent with this, K18 tumors grew faster than K14/18 tumors and more mice with K18 tumors developed lung metastases compared to mice with K14/18 tumors. However, K18 tumors arising in Si-particle irradiated mice grew even faster and were more metastatic compared to control mice. A K18 Si-irradiated host profile was enriched in genes involved in mammary stem cells, stroma, and Notch signaling. Thus systemic responses to densely ionizing radiation enriches for a ER-negative, K18-positive tumor, whose biology is more aggressive compared to similar tumors arising in non-irradiated hosts.
Publication Title
Densely ionizing radiation acts via the microenvironment to promote aggressive Trp53-null mammary carcinomas.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Accumulating data support the concept that ionizing radiation therapy (RT) has the potential to convert the tumor into an in situ, individualized vaccine; however this potential is rarely realized by RT alone. Transforming growth factor (TGF) is an immunosuppressive cytokine that is activated by RT and inhibits the antigen-presenting function of dendritic cells and the differentiation of effector CD8+ T cells. Here we tested the hypothesis that TGF hinders the ability of RT to promote anti-tumor immunity. Development of tumor-specific immunity was examined in a pre-clinical model of metastatic breast cancer.
Publication Title
TGFβ Is a Master Regulator of Radiation Therapy-Induced Antitumor Immunity.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
Identifying the functions of proteins, which define specific subnuclear structures and territories, is important for understanding eukaryotic nuclear dynamics. Sp100 is a prototypical protein of ND10/PML bodies and co-localizes with the proto-oncogenic protein PML and Daxx, proteins with critical roles in oncogenic transformation, interferon-mediated viral resistance and response to PML-directed cancer therapeutics. Sp100 isoforms contain PHD, Bromo and HMG domains and are highly sumoylated at ND10/PML bodies, all characteristics suggestive of a role in chromatin mediated gene regulation. However, no clear role for the Sp100 component of PML bodies in oncogenesis has been defined. Using isoform-specific knockdown techniques, we show that most human diploid fibroblasts, which lack Sp100, rapidly senesce and discuss gene expression changes associated with this rapid senescence.
Publication Title
Sp100 as a potent tumor suppressor: accelerated senescence and rapid malignant transformation of human fibroblasts through modulation of an embryonic stem cell program.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina mouse-6 v1.1 expression beadchip
Description
The transcription factor STAT3 is constitutively activated in tumors of different origin but the molecular bases for STAT3 addiction of tumor cells have not yet been clearly identified. We generated knock/in mice carrying the constitutively active Stat3 allele, Stat3C, and showed that Stat3C could enhance Neu oncogenic power, triggering the production of earlier onset, more invasive mammary tumors. Tumor-derived cell lines displayed higher migration and invasion and disrupted distribution of cell-cell junction markers. The tensin family member Cten (C-Terminal Tensin-like), known to mediate EGF-induced migration and highly expressed in inflammatory breast cancer, was up-regulated in both Neu;Stat3C cells and tumors. Both Cten expression and enhanced migration were strictly dependent on Stat3, and Cten silencing normalized cell migration and rescued cell-cell contact defects. Importantly, the pro-inflammatory cytokine IL-6 could mediate Cten induction in MCF10 cells, in an exquisitely Stat3-dependent way. This model allowed us to shed some light on the oncogenic role of Stat3 in the breast, suggesting moreover a mechanism through which inflammatory signals can cooperate with EGF receptors in inflammatory breast cancer.
Publication Title
Constitutively active Stat3 enhances neu-mediated migration and metastasis in mammary tumors via upregulation of Cten.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 25 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Loss of Notch1 in retinal progenitor cells (RPCs) during postnatal retinal development results in the overproduction of rod photoreceptors at the expense of interneurons and glia. To examine the molecular underpinnings of this observation, microarray analysis of singla retinal cells from wildtype (WT) or Notch1 conditional knockout (N1-CKO) retinas was performed. The majority of N1-CKO cells lost expression of known Notch target genes. These cells also had low levels of RPC and cell cycle genes, and robustly upregulated rod precursor genes. In addition, single WT cells, in which cell cycle marker genes were downregulated, expressed markers of both rod photoreceptors and interneurons. These results demonstrate that individual, newly postmitotic retinal cells can begin to differentiate into more than one cell type, and that this transitional state may be dependent on Notch1 signaling.
Publication Title
Notch1 is required in newly postmitotic cells to inhibit the rod photoreceptor fate.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Impact of mmu-miR-337-3p on the global gene expression in murine hepatoblasts.
Publication Title
MicroRNA-337-3p controls hepatobiliary gene expression and transcriptional dynamics during hepatic cell differentiation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Severe septic syndromes deeply impair innate and adaptive immunity. While neutrophils represent the first line of defense against infection, little is known about their phenotype and functions during sepsis-induced immunosuppression. The objective of this study was thus to perform for the first time a global evaluation of neutrophil alterations in immunosuppressed septic patients based on phenotypic, functional and transcriptomic studies. In addition, the potential association of these parameters and deleterious outcomes was assessed.
Publication Title
Marked alterations of neutrophil functions during sepsis-induced immunosuppression.
Sample Metadata Fields
Disease
View Samples- Homo sapiens
- 120 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Sepsis is a major health concern, with high morbidity and mortality workdwide. In order to identify prognostic biomarkers in septic shock patients, we performed a microarray study exploring the early modulation of gene expression according to day 28 mortality.
Publication Title
Modulation of LILRB2 protein and mRNA expressions in septic shock patients and after ex vivo lipopolysaccharide stimulation.
Sample Metadata Fields
Sex, Age, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
NextSeq 500
Description
We performed a 3' RACE of a novel HIV RNA TAR-gag in order to determine the sequence of the RNA at the 3' end. Our data had shown that TAR-gag was potentially a noncoding RNA and our hypothesis was that TAR-gag ended somewhere prior to the end of the gag region of the HIV genome. The 3' RACE experiment showed that TAR-gag actually consists of four different RNA clusters, the longest of which ends at 615 bases from the transcription start site; this is in the middle of the p17 region of the gag gene. In addition, we sequenced all host RNAs in the EVs. Overall design: RNA from J1.1 and U1 exosomes was isolated and converted to cDNA. Sequencing libraries of the cDNA were made and a 3' RACE was perforemed to determine how long TAR-gag RNA is. Please note that the clustering analysis (published in PMID 28536264) was done only on the unfragmented samples (i.e. *-U samples).
Publication Title
An Omics Approach to Extracellular Vesicles from HIV-1 Infected Cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Saccharomyces cerevisiae
- 4 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Rsp5 is an essential and multi-functional E3 ubiquitin ligase in Saccharomyces cerevisiae. We previously isolated the Ala401Glu rsp5 mutant, which is hypersensitive to various stresses. To understand the function of Rsp5 in stress responses, suppressor genes whose overexpression allows rsp5A401E cells to grow at high temperature were screened. The KIN28 and POG1 genes, encoding a subunit of the transcription factor TFIIH and a putative transcriptional activator, respectively, were identified as multicopy suppressors of not only high temperature but also LiCl stresses. The overexpression of Kin28 and Pog1 in rsp5A401E cells caused an increase in the transcriptional level of some stress proteins when exposed to temperature up-shift. DNA microarray analysis under LiCl stress revealed that the transcriptional level of some proteasome components was increased in rsp5A401E cells overexpressing Kin28 or Pog1. These results suggest that the overexpression of Kin28 and Pog1 enhances the protein refolding and degradation pathways in rsp5A401E cells.
Publication Title
Overexpression of two transcriptional factors, Kin28 and Pog1, suppresses the stress sensitivity caused by the rsp5 mutation in Saccharomyces cerevisiae.
Sample Metadata Fields
No sample metadata fields
View Samples