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GSE32239
Mus musculus
22 Downloadable Samples
Affymetrix Mouse Expression 430A Array (moe430a)
Description
The ability of oncogenes to provoke cancer is harnessed by regulators that control cell proliferation or induce apoptosis, and bypass of these checkpoints is a hallmark of malignancies. Myc oncoproteins are overexpressed in ~70% of all cancers and induce numerous transcription targets that regulate cell growth, metabolism, and the ribosome machinery. We used the E-Myc mouse model from which one can directly compare expression profiles of wild type versus Myc-expressing B220+ pre-malignant lymphocytes and also queried differences in gene expression that ensue following the neoplastic switch to lymphoma (Nilsson et al., 2005 - PMID:15894264 and Keller et al. 2010 - PMID:20598117).
Publication Title
Targeting ornithine decarboxylase in Myc-induced lymphomagenesis prevents tumor formation.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 9 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Background: The ability of an organism to repair damages to DNA is inextricably linked to aging and cancer. We have characterized and compared the transcriptome of C. elegans mutants deficient in DNA base excision repair, nucleotide excision repair or both to elucidate the transcriptional changes incurred by the reduction of these repair pathways.
Publication Title
A two-tiered compensatory response to loss of DNA repair modulates aging and stress response pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
The nematode Caenorhabditis elegans has been used extensively to study responses to DNA damage. In contrast, little is known about DNA repair in this organism. C. elegans is unusual in that it encodes few DNA glycosylases and the uracil-DNA glycosylase (UDG) encoded by the ung-1 gene is the only known UDG. C. elegans could therefore become a valuable model organism for studies of the genetic interaction networks involving base excision repair (BER). As a first step towards characterization of BER in C. elegans, we show that the UNG-1 protein is an active uracil-DNA glycosylase. We demonstrate that an ung-1 mutant has reduced ability to repair uracil-containing DNA but that an alternative Ugi-inhibited activity is present in ung-1 nuclear extracts. Finally, we demonstrate that ung-1 mutants show altered levels of apoptotic cell corpses formed in response to DNA damaging agents. Increased apoptosis in the ung-1 mutant in response to ionizing radiation (IR) suggests that UNG-1 contributes to repair of IR-induced DNA base damage in vivo. Following treatment with paraquat however, the apoptotic corpse-formation was reduced. Gene expression profiling suggests that this phenotype is a consequence of compensatory transcriptomic shifts that modulate oxidative stress responses in the mutant and not an effect of reduced DNA damage signaling.
Publication Title
Loss of Caenorhabditis elegans UNG-1 uracil-DNA glycosylase affects apoptosis in response to DNA damaging agents.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip, Illumina MouseRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Defective mitophagy in XPA via PARP-1 hyperactivation and NAD(+)/SIRT1 reduction.
Sample Metadata Fields
Sex, Cell line, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip
Description
Mitochondrial dysfunction is a common feature in neurodegeneration and aging. We identify mitochondrial dysfunction in xeroderma pigmentosum group A (XPA), a nucleotide excision DNA repair disorder with severe neurodegeneration, in silico and in vivo. XPA deficient cells show defective mitophagy with excessive cleavage of PINK1 and increased mitochondrial membrane potential. The mitochondrial abnormalities appear to be caused by decreased activation of the NAD+-SIRT1-PGC-1 axis triggered by hyperactivation of the DNA damage sensor PARP1. This phenotype is rescued by PARP1 inhibition or by supplementation with NAD+ precursors that also rescue the lifespan defect in xpa-1 nematodes. Importantly, this pathogenesis appears common to ataxia-telangiectasia and Cockayne syndrome, two other DNA repair disorders with neurodegeneration, but absent in XPC, a DNA repair disorder without neurodegeneration. Our findings reveal a novel nuclear-mitochondrial cross-talk that is critical for the maintenance of mitochondrial health.
Publication Title
Defective mitophagy in XPA via PARP-1 hyperactivation and NAD(+)/SIRT1 reduction.
Sample Metadata Fields
Sex, Treatment
View Samples- Caenorhabditis elegans
- 8 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
We demonstrate that transcriptomic profiling of the NER mutant ercc-1 offers better understanding of the complex phenotypes of ercc-1 deficiency in C. elegans, as it does in mammalian models. There is a transcriptomic shift in ercc-1 mutants that suggests a stochastic impairment of growth and development, with a shift towards a higher proportion of males in the population. Extensive phenotypic analyses confirm that NER deficiency in C. elegans leads to severe developmental and growth defects and a reduced replicative lifespan, although post-mitotic lifespan is not affected. Results suggest that these defects are caused by an inability to cope with randomly occurring DNA damage, which may interfere with transcription and replication.
Publication Title
DNA damage leads to progressive replicative decline but extends the life span of long-lived mutant animals.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
NF1-C2 suppresses tumorigenesis and epithelial-to-mesenchymal transition by repressing FoxF1.
Publication Title
Forkhead Box F1 promotes breast cancer cell migration by upregulating lysyl oxidase and suppressing Smad2/3 signaling.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Caenorhabditis elegans
- 43 Downloadable Samples
Illumina HiSeq 1500, Illumina Genome Analyzer IIx
Description
C. elegans totalRNA profiles of worms treated with RNAi for different Integrator complex genes or L4440 (Control). Worms were grown at 15ºC and samples were taken six days after silencing Overall design: C. elegans totalRNA profiles of worms treated with RNAi for different Integrator complex genes or L4440 (Control). Three replicates per sample. Deep sequencing in Illumina HiSeq1500.
Publication Title
Disruption of the Caenorhabditis elegans Integrator complex triggers a non-conventional transcriptional mechanism beyond snRNA genes.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 20 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Tumor hypoxia levels range from mild to severe and have different biological and therapeutical consequences, but are not easily assessable in patients. We present a method based on diagnostic dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) that visualizes a continuous range of hypoxia levels in tumors of cervical cancer patients. Hypoxia images were generated using an established approach based on pixel-wise combination of the DCE-MRI parameters e and Ktrans, reflecting oxygen consumption and supply, respectively. An algorithm to retrieve hypoxia levels from the images was developed and validated in 28 xenograft tumors, by comparing the MRI-defined levels with hypoxia levels derived from pimonidazole stained histological sections. We further established an indicator of hypoxia levels in patient tumors based on expression of nine hypoxia responsive genes. A strong correlation was found between these indicator values and the MRI-defined hypoxia levels in 63 patients. Chemoradiotherapy outcome of 74 patients was most strongly predicted by moderate hypoxia levels, whereas more severe or milder levels were less predictive. By combining gene expression profiles and MRI-defined hypoxia levels in cancer hallmark analysis, we identified a distribution of levels associated with each hallmark; oxidative phosphorylation and G2/M checkpoint were associated with moderate hypoxia, and epithelial-to-mesenchymal transition and inflammatory responses with significantly more severe levels. At the mildest levels, interferon response hallmarks, together with stabilization of HIF1A protein by immunohistochemistry, appearred significant. Thus, our method visualizes the distribution of hypoxia levels within patient tumors and has potential to distinguish levels of different prognostic and biological significance.
Publication Title
MRI Distinguishes Tumor Hypoxia Levels of Different Prognostic and Biological Significance in Cervical Cancer.
Sample Metadata Fields
Cell line, Treatment
View Samples- Rattus norvegicus
- 27 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Primordial follicle assembly is the process by which ovarian primordial follicles are formed. During follicle assembly oocyte nests break down and a layer of pre-granulosa cells surrounds individual oocytes to form primordial follicles. The pool of primordial follicles formed is the source of oocytes for ovulation during a females reproductive life. Complex networks of cellular signaling and gene expression are essential for any biological process. A systems biology experimental approach provides a global view of these gene relationships in a particular developmental process. The current study utilized a systems approach to detect all genes that are differentially expressed in response to seven different growth factor and hormone treatments known to influence primordial follicle assembly in a neonatal rat ovary culture system. One novel growth factor, basic fibroblast growth factor (FGF2), was experimentally determined to inhibit follicle assembly. The different growth factor and hormone treatments were all found to affect the same physiological pathways, but each treatment affected a unique set of differentially expressed genes (signature gene set). A gene bionetwork analysis identified gene modules of coordinately expressed interconnected genes and it was found that different gene modules appear to accomplish distinct tasks during primordial follicle assembly. Unique gene networks were identified for a number of the modules and signature gene sets. Predictions of physiological pathways important to follicle assembly were validated using ovary culture experiments in which ERK1/2 (MAPK1) activity was increased. A number of the highly interconnected genes in these gene networks have previously been linked to primary ovarian insufficiency (POI) and polycystic ovarian disease syndrome (PCOS). Observations have identified novel factors and gene networks that regulate primordial follicle assembly. This systems approach has helped elucidate the molecular control of primordial follicle assembly and provided potential therapeutic targets for the treatment of ovarian disease.
Publication Title
Gene bionetworks that regulate ovarian primordial follicle assembly.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples