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GSE51358
Mus musculus
16 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Ha-ras and β-catenin oncoproteins orchestrate metabolic programs in mouse liver tumors.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The process of hepatocarcinogenesis in the diethylnitrosamine (DEN) initiation/phenobarbital (PB) promotion mouse model involves the selective clonal outgrowth of cells harboring oncogene mutations in Ha-ras, B-raf, or Ctnnb1. Here, we have characterized mouse liver tumors harboring either Ctnnb1 or Ha-ras mutations via integrated molecular profiling at the transcriptional and translational and post-translational levels. In addition, metabolites of the intermediary metabolism were quantified by high resultion 1H magic angle nuclear magnetic resonance (HR-MAS NMR). We have identified tumor characteristic genotype-specific differences in mRNA and miRNA expression, protein levels, and post-translational modifications and in metabolite levels that facilitate the molecular and biochemical stratification of tumor phenotypes. Bioinformatic integration of these data at the pathway level led to novel insights into tumor genotype-specific aberrant cell signaling and in particular to a better understanding of alterations in pathways of the cell intermediary metabolism, which are driven by the constitutive activation of the -Catenin and Ha-ras oncoproteins in tumors of the two genotypes.
Publication Title
Ha-ras and β-catenin oncoproteins orchestrate metabolic programs in mouse liver tumors.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 345 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Rat Expression 230A Array (rae230a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Phenobarbital induces cell cycle transcriptional responses in mouse liver humanized for constitutive androstane and pregnane x receptors.
Sample Metadata Fields
Age, Specimen part, Treatment, Subject, Time
View Samples- Mus musculus
- 167 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcino- genesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences in receptor-dependent mechanisms underlying liver tissue molecular responses to PB. Early and late transcriptomic responses to sustained PB exposure were investigated in liver tissue from double knock-out CAR and PXR (CARKO -PXRKO ), double humanized CAR and PXR (CARh - PXRh), and wild-type C57BL/6 mice. Wild-type and CARh-PXRh mouse livers exhibited temporally and quantitatively similar tran- scriptional responses during 91 days of PB exposure including the sustained induction of the xenobiotic response gene Cyp2b10, the Wnt signaling inhibitor Wisp1, and noncoding RNA biomarkers from the Dlk1-Dio3 locus. Transient induction of DNA replication (Hells, Mcm6, and Esco2) and mitotic genes (Ccnb2, Cdc20, and Cdk1) and the proliferation-related nuclear antigen Mki67 were ob- served with peak expression occurring between 1 and 7 days PB ex- posure. All these transcriptional responses were absent in CARKO- PXRKO mouse livers and largely reversible in wild-type and CARh - PXRh mouse livers following 91 days of PB exposure and a subse- quent 4-week recovery period. Furthermore, PB-mediated upregu- lation of the noncoding RNA Meg3, which has recently been associ- ated with cellular pluripotency, exhibited a similar dose response and perivenous hepatocyte-specific localization in both wild-type and CARh-PXRh mice. Thus, mouse livers coexpressing human CAR and PXR support both the xenobiotic metabolizing and the proliferative transcriptional responses following exposure to PB.
Publication Title
Phenobarbital induces cell cycle transcriptional responses in mouse liver humanized for constitutive androstane and pregnane x receptors.
Sample Metadata Fields
Age, Specimen part, Treatment, Subject, Time
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
To determine a gene/molecular fingerprint of multiple myeloma (MM) endothelial cells (MMECs), also identifying some of the vascular mechanisms that govern the malignant progression from quiescent monoclonal gammopathy of undetermined significance (MGUS). A comparative gene expression profiling (GEP) was carried out on patient-derived MMECs and MGUS endothelial cells (MGECs) using the Affymetrix U133A Arrays. Expression of selective vascular markers were also validated by RT-PCR and immunoblotting analysis in primary cultures of ECs isolated from total bone marrow (BM)-mononuclear cells. Twenty-two genes were found differently expressed in MMECs compared to MGECs (with 14 down-regulated and 8 up-regulated), thus proving that molecular differences were maintained in vitro. Specific pathways analysis revealed transcriptional and protein expression changes for key regulators of extracellular matrix formation and bone remodeling, cell-adhesion, chemotaxis, angiogenesis, resistance to apoptosis, and cell-cycle regulation. Specifically, we focused on six of these genes (DIRAS3, SERPINF1, SRPX, BNIP3, IER3 and SEPW1), which were not previously functionally correlated to the overangiogenic phenotype of MMECs and disease activity. These data identified distinct EC gene expression profiles and some vascular phenotypes that could influence the remodeling of the BM-microenvironment in patients with active MM. A better understanding of the linkage between genetic and epigenetic events in MM tumor/ECs may contribute to the molecular classification of the disease, thereby identifying selective targets of more effective anti-vessel/stroma therapeutic strategies.
Publication Title
Gene expression profiling of bone marrow endothelial cells in patients with multiple myeloma.
Sample Metadata Fields
Sex
View Samples- Sus scrofa
- 24 Downloadable Samples
- Porcine Gene 1.1 ST Array (porgene11st)
Description
An early settlement of a complex gut microbiota can protect against gastro-intestinal dysbiosis, but the effects of neonatal microbiota colonization and early life feeding of medium chain triglycerides on the maturation of the porcine gastric mucosa are largely unknown.
Publication Title
The effects of starter microbiota and the early life feeding of medium chain triglycerides on the gastric transcriptome profile of 2- or 3-week-old cesarean delivered piglets.
Sample Metadata Fields
Specimen part
View Samples- Sus scrofa
- 12 Downloadable Samples
- Porcine Gene 1.1 ST Array (porgene11st)
Description
An early settlement of a complex gut microbiota can protect against gastro-intestinal dysbiosis, but the effects of neonatal microbiota colonization on the maturation of the porcine gastric mucosa are largely unknown.
Publication Title
The effects of starter microbiota and the early life feeding of medium chain triglycerides on the gastric transcriptome profile of 2- or 3-week-old cesarean delivered piglets.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 18 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Arabidopsis plants were treated either with mock or MSB (0.2 mM of Menadione sodium bisulphite). <br></br>Tissue was sampled after 3, 6 and 24 hours.
Publication Title
Molecular analysis of menadione-induced resistance against biotic stress in Arabidopsis.
Sample Metadata Fields
Age, Specimen part, Compound, Time
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Bone is a frequent target of lung cancer metastasis, which is associated with significant morbidity and a dismal prognosis. To identify and functionally characterize genes involved in the mechanisms of osseous metastasis we developed a murine lung cancer model. Comparative transcriptomic analysis identified genes encoding signaling molecules (such as TCF4 and PRKD3), and cell anchorage related proteins (MCAM, and SUSD5), some of which were basally modulated by TGFbeta in tumor cells and in conditions mimicking tumor-stroma interactions. Triple gene combinations induced not only high osteoclastogenic activity but also a marked enhancement of global metalloproteolytic activities in vitro. These effects were strongly associated with robust bone colonization in vivo, whereas this gene subset was ineffective in promoting local tumor growth and cell homing activity to bone. Interestingly, global inhibition of metalloproteolytic activities and simultaneous TGFbeta blockade in vivo led to increased survival and a remarkable attenuation of bone tumor burden and osteolytic metastasis. Thus, this metastatic gene signature mediates bone-matrix degradation by a dual mechanism of induction of TGFbeta-dependent osteoclastogenic bone resorption and enhancement of stroma-dependent metalloproteolytic activities. Our findings suggest the cooperative contribution of host-derived and cell-autonomous effects directed by a small subset of genes in mediating aggressive osseous colonization.
Publication Title
A novel lung cancer signature mediates metastatic bone colonization by a dual mechanism.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 69 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The molecular events during nongenotoxic carcinogenesis and their temporal order are poorly understood but thought to include long-lasting perturbations of gene expression. Here, we have investigated the temporal sequence of molecular and pathological perturbations at early stages of phenobarbital (PB) mediated liver tumor promotion in vivo. Molecular profiling (mRNA, microRNA [miRNA], DNA methylation, and proteins) of mouse liver during 13 weeks of PB treatment revealed progressive increases in hepatic expression of long noncoding RNAs and miRNAs originating from the Dlk1-Dio3 imprinted gene cluster, a locus that has recently been associated with stem cell pluripotency in mice and various neoplasms in humans. PB induction of the Dlk1-Dio3 cluster noncoding RNA (ncRNA) Meg3 was localized to glutamine synthetase-positive hypertrophic perivenous hepatocytes, sug- gesting a role for -catenin signaling in the dysregulation of Dlk1-Dio3 ncRNAs. The carcinogenic relevance of Dlk1-Dio3 locus ncRNA induction was further supported by in vivo genetic dependence on constitutive androstane receptor and -catenin pathways. Our data identify Dlk1-Dio3 ncRNAs as novel candidate early biomarkers for mouse liver tumor promotion and provide new opportunities for assessing the carcinogenic potential of novel compounds.
Publication Title
Identification of Dlk1-Dio3 imprinted gene cluster noncoding RNAs as novel candidate biomarkers for liver tumor promotion.
Sample Metadata Fields
Specimen part
View Samples