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GSE15694
Mus musculus
18 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
The Dbl family of proteins represents a large group of proto-oncogenes involved in cell growth regulation. Alterations of the normal function of these proteins lead to pathological processes such as developmental disorders and neoplastic transformation. We have generated transgenic mice introducing the onco-Dbl cDNA sequences linked to the metallothionein promoter into the germ line of FVB mice and found that onco-Dbl expression affected proliferation, migration and differentiation of lens epithelial cells. We used high density oligonucleotide microarray to define the transcriptional profile induced by Dbl in the lenses of transgenic mice and observed modulation of genes encoding proteins promoting epithelial-mesenchymal transition (EMT). Moreover, genes encoding proteins involved in the positive regulation of apoptosis were markedly down regulated while anti-apoptotic genes were strongly up-regulated. Finally, several genes encoding proteins involved in the process of angiogenesis were up-regulated. These observations were validated by histological and immunohistochemical examination of the transgenic lenses, where vascularization can be readily observed. Thus, onco-Dbl expression in mouse lenses induces disruption of the lens architecture, epithelial cell proliferation, EMT, evasion from cell death, and aberrant angiogenesis.
Publication Title
Induction of epithelial mesenchimal transition and vasculogenesis in the lenses of Dbl oncogene transgenic mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Hepatocellular carcinoma (HCC) represents a major health problem as it afflicts an increasing number of patients worldwide. Albeit most of the risk factors for HCC are known, this is a deadly syndrome with a life expectancy at the time of diagnosis of less than 1 year. Definition of the molecular principles governing the neoplastic transformation of the liver is an urgent need to facilitate the clinical management of patients, based on innovative methods to detect the disease in its early stages and on more efficient therapies. In the present study we have combined the analysis of a murine model and human samples of HCC to identify genes differentially expressed early in the process of hepatocarcinogenesis, using a microarray based approach. Expression of 190 genes was impaired in murine HCC from which 65 were further validated by low-density array RT PCR. The expression of the best 45 genes was then investigated in human samples resulting in 18 genes which expression was significantly modified in HCC. Among them, JUN, methionine adenosyltransferase 1A and 2A, phosphoglucomutase 1, and acyl CoA dehydrogenase short branched chain indicate defective cell proliferation as well as one carbon pathway, glucose and fatty acid metabolism, both in HCC and cirrhotic liver, a well known preneoplastic condition. These alterations were further confirmed in public transcriptomic datasets from other authors. In addition, vasodilator stimulated phosphoprotein, an actin-associated protein involved in cytoskeleton remodelling, was also found to be increased in the liver and serum of cirrhotic and HCC patients. In addition to revealing the impairment of central metabolic pathways for liver homeostasis, further studies may probe the potential value of the reported genes for the early detection of HCC.
Publication Title
A signature of six genes highlights defects on cell growth and specific metabolic pathways in murine and human hepatocellular carcinoma.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
HRE1 and HRE2 are two ERF transcription factors induced by low oxygen. In this work we analyzed the effect of ectopic expression of HRE1 and HRE2 on the arabidopsis transcriptome in aerobic and hypoxic (1% O2) conditions. While HRE1 has a moderate effect on the expression of anaerobic genes under hypoxia, HRE2 does not affect them either under aerobic or hypoxic conditions.
Publication Title
HRE1 and HRE2, two hypoxia-inducible ethylene response factors, affect anaerobic responses in Arabidopsis thaliana.
Sample Metadata Fields
Age, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Experiment with 6 hybridizations, using 30 samples of species [Homo sapiens], using 6 arrays of array design [Affymetrix GeneChip Human Genome HG-U133A [HG-U133A]], producing 6 raw data files and 6 transformed and/or normalized data files.
Publication Title
Hypoxia modifies the transcriptome of primary human monocytes: modulation of novel immune-related genes and identification of CC-chemokine ligand 20 as a new hypoxia-inducible gene.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Organ transplant recipients (OTRs) on Cyclosporine A (CSA) are prone to catastrophic cutaneous squamous cell carcinoma (SCC). Allograft-sparing, cancer-targeting systemic treatments are unavailable. We have shown increased risk for catastrophic SCC in OTRs via CSA-mediated induction of Interleukin-22 (IL-22). Herein, we found CSA drives SCC proliferation and tumor growth through IL-22 and JAK/STAT pathway induction. We in turn inhibited SCC growth with an FDA-approved JAK 1/2 inhibitor, Ruxolitinib. In human SCC cells, greatest proliferative response to IL-22 and CSA treatment occurred in non-metastasizing lines. IL-22 treatment upregulated JAK1 and STAT1/3 in A431 SCC cells. JAK/STAT pathway genes were highly expressed in tumors from a cohort of CSA-exposed OTRs, and in SCC with high risk for metastasis. Compared to immunocompetent SCC, genes associated with innate immunity, response to DNA damage and p53 regulation were differentially expressed in SCC from OTRs. In nude mice engrafted with human A431 cells, IL-22 and CSA treatment increased tumor growth and upregulated IL-22 receptor, JAK1 and STAT 1/3 expression. Ruxolitinib treatment significantly reduced tumor volume and reversed the accelerated tumor growth. CSA and IL-22 exacerbate aggressive behavior in SCC. Targeting the IL-22 axis via selective JAK/STAT inhibition may reduce the progression of aggressive SCC in OTRs, without compromising immunosuppression.
Publication Title
Ruxolitinib inhibits cyclosporine-induced proliferation of cutaneous squamous cell carcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
Illumina HiSeq 2500
Description
Bulk RNA sequencing data from neural progenitor cells under conditions of low or high growth factor and Notch pathway activation Overall design: Cells were treated with high (20 ng/ml EGF and FGF) or low (0.5 ng/ml EGF) recombinant growth factors, with or without Notch pathway inhibitor (DAPT, 10 uM) for 12h.
Publication Title
<i>Cis-</i>activation in the Notch signaling pathway.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Specific vulnerability of neurons in the human entorhinal cortex has been associated with the onset of disease.
Publication Title
Differential gene expression analysis of human entorhinal cortex support a possible role of some extracellular matrix proteins in the onset of Alzheimer disease.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 4 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We treated Arabidopsis seedlings with chitosan and carried out a transcript profiling analysis (GeneChip microarrays) in order to identify genes and transcription factors regulated by chitosan. The results showed that jasmonate and defense responsive genes, camalexin and lignin biosynthetic genes were among genes up-regulated by chitosan. Several transcription factors are also strongly induced by chitosan.
Publication Title
Transcript profiling of chitosan-treated Arabidopsis seedlings.
Sample Metadata Fields
Age, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2000
Description
An unbalanced karyotype, a condition known as aneuploidy, has a profound impact on cellular physiology and is a hallmark of cancer. Determining how aneuploidy affects cells is thus critical to understanding tumorigenesis. Here we show that aneuploidy interferes with the degradation of autophagosomes within lysosomes. Mis-folded proteins that accumulate in aneuploid cells due to aneuploidy-induced proteomic changes overwhelm the lysosome with cargo, leading to the observed lysosomal degradation defects. Importantly, aneuploid cells respond to lysosomal saturation. They activate a lysosomal stress pathway that specifically increases the expression of genes needed for autophagy-mediated protein degradation. Our results reveal lysosomal saturation as a universal feature of the aneuploid state that must be overcome during tumorigenesis. Overall design: RPE-1 cells either untreated or treated with one of Reversine, Bafilomycin A1 or MG132, each condition was done in triplicate. D14-*_Control: untreated control D14-*_Rev: cells treated with 0.5uM Reversine for 24hrs and harvested 48hrs later D14-*_Baf: cells treated with 0.1uM BafA1 for 6hrs D14-*_Mg: cells treated with 1uM MG132 for 24 hrs
Publication Title
Aneuploidy-induced cellular stresses limit autophagic degradation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 21 Downloadable Samples
- Illumina HiSeq 2500
Description
The aim of this study was to establish an in vitro model to investigate the initial stages of human implantation based on co-culture of a) immortalized cells representing the receptive (Ishikawa) or non-receptive (HEC-1-A) endometrial epithelium with b) spheroids of a trophoblastic cell line (JEG-3) modified to express green fluorescent protein. After co-culturing Ishikawa cells with trophoblast spheroids, 310 and 298 genes increased or decreased their expression compared to non-co-cultured Ishikawa control cells, respectively; only 9 genes (5 increased and 4 decreased) were differentially expressed in HEC-1-A upon co-culture with trophoblast spheroids. Compared to HEC-1-A, the trophoblast challenge to Ishikawa cells differentially regulated the expression of 495 genes. In summary, upon co-culture with the trophoblast spheroids, non-receptive epithelium is characterized by a muted transcriptional response which in turn fails to activate the full transcriptional response that trophoblast spheroids undergo when co-cultured with receptive epithelium. Overall design: GFP expressing JEG-3 spheroids were co-cultured with confluent monolayers of receptive Ishikawa or non-receptive HEC-1-A epithelia. After 48 hours of co-culture, GFP+ (trophoblast JEG-3 spheroid cells) and GFP- cell fractions (receptive Ishikawa or non-receptive HEC-1-A epithelial cells) were isolated by fluorescence-activated flow cytometry (FACS). The specific transcriptional changes of the isolated cell populations were analyzed by RNA-seq profiling. Statistical significance of gene expression differences was set at an absolute log2 fold change (log2FC) =1 and an adjusted p-value <0.05.
Publication Title
Transcriptomic analysis of the interaction of choriocarcinoma spheroids with receptive vs. non-receptive endometrial epithelium cell lines: an in vitro model for human implantation.
Sample Metadata Fields
Specimen part, Subject
View Samples