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GSE14337
Rattus norvegicus
6 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The MUC1 oncoprotein is aberrantly overexpressed in diverse human malignancies including breast and lung cancer. Although MUC1 modulates the activity of several transcription factors, there is no information regarding the effects of MUC1 on global gene expression patterns and the potential role of MUC1-induced genes in predicting outcome for cancer patients. We have developed an experimental model of MUC1-induced transformation that has identified the activation of gene families involved in oncogenesis, angiogenesis and extracellular matrix remodeling. A set of experimentally-derived MUC1-induced genes associated with tumorigenesis was applied to the analysis of breast and lung adenocarcinoma cancer databases. A 35-gene MUC1-induced tumorigenesis signature (MTS) predicts significant decreases in both disease-free and overall survival in patients with breast (n = 295) and lung (n = 442) cancers. The data demonstrate that the MUC1 oncoprotein contributes to the regulation of genes that are highly predictive of clinical outcome in breast and lung cancer patients.
Publication Title
MUC1-induced alterations in a lipid metabolic gene network predict response of human breast cancers to tamoxifen treatment.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Endothelial inflammation contributes to the pathogenesis of numerous human diseases; however, the role of tumor endothelial inflammation in the growth of experimental tumors and its influence on the prognosis of human cancers is less understood. TNF-, an important mediator of tumor stromal inflammation, is known to target the tumor vasculature. In this study, we demonstrate that B16-F1 melanomas grew more rapidly in C57BL/6 wild-type (WT) mice than in syngeneic mice with germline deletions of both TNF- receptors (KO). This enhanced tumor growth was associated with increased COX2 inflammatory expression in WT tumor endothelium compared to endothelium in KO mice. We purified endothelial cells from WT and KO tumors and characterized dysregulated gene expression, which ultimately formed the basis of a 6-gene Inflammation-Related Endothelial-derived Gene (IREG) signature. This inflammatory signature expressed in WT tumor endothelial cells was trained in human cancer datasets and predicted a poor clinical outcome in breast cancer, colon cancer, lung cancer and glioma. Consistent with this observation, conditioned media from human endothelial cells treated with pro-inflammatory cytokines (TNF- and interferons) accelerated the growth of human colon and breast tumors in immune-deprived mice as compared with conditioned media from untreated endothelial cells. These findings demonstrate that activation of endothelial inflammatory pathways contributes to tumor growth and progression in diverse human cancers.
Publication Title
Tumor endothelial inflammation predicts clinical outcome in diverse human cancers.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
Illumina HiSeq 2500
Description
We created two cell lines derived from Ovcar8 by stably transfecting with an eGFP-firefly luciferase fusion protein and either an additional copy of the gene TWIST1 or an shRNA against TWIST1, under the control of the CMV promoter. RNA sequencing was used to look for differential expression of genes that may impact cisplatin resistance in epithelial ovarian cancer. Overall design: RNA-seq for differential expression between two cell lines differing in expression of gene of interest. Run as biological replicates and technical triplicates.
Publication Title
TWIST1 drives cisplatin resistance and cell survival in an ovarian cancer model, via upregulation of GAS6, L1CAM, and Akt signalling.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Affymetrix Mouse Gene 1.0 ST Array profiles were generated from acticular cartilage derived from CBA and Str/ort mice at three ages (8W, 18W, 40W), corresponding to stages prior to, at and late after natural osteoarthritis (OA) onset in OA-prone Str/ort mice.
Publication Title
Time-series transcriptional profiling yields new perspectives on susceptibility to murine osteoarthritis.
Sample Metadata Fields
Age, Specimen part
View Samples- Rattus norvegicus
- 8 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Here we tested a hypothesis that epileptogenesis influences expression pattern of genes in the basolateral amygdala that are critical for fear conditioning. Whole genome molecular profiling of basolateral rat amygdala was performed to compare the transcriptome changes underlying fear learning in epileptogenic and control animals. Our analysis revealed that after acquisition of fear conditioning 26 genes were regulated differently in the basolateral amygdala of both groups. Thus, our study provides the first evidence that not only the damage to the neuronal pathways but also altered composition or activity level of molecular machinery responsible for formation of emotional memories within surviving pathways can contribute to impairment in emotional learning in epileptogenic animals. Understanding the function of those genes in emotional learning provides an attractive avenue for identification of novel drug targets for treatment of emotional disorders after epileptogenesis-inducing insult.
Publication Title
Epileptogenesis alters gene expression pattern in rats subjected to amygdala-dependent emotional learning.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 74 Downloadable Samples
- NextSeq 500
Description
Macrophages, dendritic cells, conventional CD4+ T cells, CD8+ T cells, and regulatory T cells isolated from mouse colon cancer model MC38 tumors implanted subcutaneously to young (3 month) and aged (12 month) mice were sequenced using ImmGen's standard ultra-low input RNA-seq pipeline, in order to study age-dependent differences in intraltumoral immune cell functions and their impact on tumor control Overall design: Samples collected at the Center for Systems Biology at Mass General Hospital, shipped frozen to a central location, and sequenced using ImmGen's standard RNA-seq pipeline
Publication Title
Age-related tumor growth in mice is related to integrin α 4 in CD8+ T cells.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Rattus norvegicus
- 30 Downloadable Samples
- Illumina HiSeq 2000, Illumina Genome Analyzer IIx
Description
TBI was induced with lateral fluid-percussion injury in adult male rats. Genome-wide RNA-seq of the perilesional cortex, ipsilateral thalamus and dorsal hippocampus was performed at 3 months post-TBI. The data highlighted chronic transcriptional changes, particularly, in the perilesional cortex and thalamus. Genes showing a significantly altered expression both in the cortex and thalamus were submitted to the LINCS web query to identify novel pharmacotherapies to improve post-TBI outcome. Overall design: TBI was induced to 5 rats, 5 sham operated served as a controls.
Publication Title
Analysis of Post-Traumatic Brain Injury Gene Expression Signature Reveals Tubulins, Nfe2l2, Nfkb, Cd44, and S100a4 as Treatment Targets.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Poorly differentiated thyroid carcinomas (PDTC) represent a heterogeneous, aggressive entity, presenting features that suggest a progression from well-differentiated carcinomas.
Publication Title
Gene expression profiling associated with the progression to poorly differentiated thyroid carcinomas.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Rattus norvegicus
- 15 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
OBJECTIVE: To analyze genome-wide changes in chondrocyte gene expression in a surgically induced model of early osteoarthritis (OA) in rats, to assess the similarity of this model to human OA, and to identify genes and mechanisms leading to OA pathogenesis. METHODS: OA was surgically induced in 5 rats by anterior cruciate ligament transection and partial medial meniscectomy. Sham surgery was performed in 5 additional animals, which were used as controls. Both groups underwent 4 weeks of forced mobilization, 3 times per week. RNA was extracted directly from articular chondrocytes in the OA (operated), contralateral, and sham-operated knees. Affymetrix GeneChip expression arrays were used to assess genome-wide changes in gene expression. Expression patterns of selected dysregulated genes, including Col2a1, Mmp13, Adamts5, Ctsc, Ptges, and Cxcr4, were validated by real-time polymerase chain reaction, immunofluorescence, or immunohistochemistry 2, 4, and 8 weeks after surgery. RESULTS: After normalization, comparison of OA and sham-operated samples showed 1,619 differentially expressed probe sets with changes in their levels of expression >/=1.5-fold, 722 with changes >/=2-fold, 135 with changes >/=4-fold, and 20 with changes of 8-fold. Dysregulated genes known to be involved in human OA included Mmp13, Adamts5, and Ptgs2, among others. Several dysregulated genes (e.g., Reln, Phex, and Ltbp2) had been identified in our earlier microarray study of hypertrophic chondrocyte differentiation. Other genes involved in cytokine and chemokine signaling, including Cxcr4 and Ccl2, were identified. Changes in gene expression were also observed in the contralateral knee, validating the sham operation as the appropriate control. CONCLUSION: Our results demonstrate that the animal model mimics gene expression changes seen in human OA, supporting the relevance of newly identified genes and pathways to early human OA. We propose new avenues for OA pathogenesis research and potential targets for novel OA treatments, including cathepsins and cytokine, chemokine, and growth factor signaling pathways, in addition to factors controlling the progression of chondrocyte differentiation.
Publication Title
Global analyses of gene expression in early experimental osteoarthritis.
Sample Metadata Fields
No sample metadata fields
View Samples- Gallus gallus
- 12 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
The proneural NEUROG2 is essential for neuronal commitment, cell cycle exit and neuronal differentiation. Characterizing genes networks regulated downstream of NEUROG2 is therefore of prime importance. To identify NEUROG2 early response genes, we combined gain of function in the neural tube with a global detection of modified transcripts using microarrays. We included in our study a mutant form of NEUROG2 (NEUROG2AQ) that cannot bind DNA and cannot trigger neurogenesis. Using this approach, we identified 942 genes modified at the onset of NEUROG2 activation. The global analysis of functions regulated by NEUROG2 allowed unmasking its rapid impact on cell cycle control. We found that NEUROG2 specifically represses a subset of cyclins acting at the G1 and S phases of the cell cycle, thereby impeding S phase re-entry. This repression occurs before modification of p27kip1, indicating that the decision to leave the cell cycle precedes the activation of this Cyclin-dependant Kinase Inhibitor. Moreover, NEUROG2 down-regulates only one of the D-type cyclins, cyclinD1, and maintaining cyclinD1 blocks the ability of the proneural to trigger cell cycle exit, without altering its capacity to trigger neuronal differentiation. The fact that NEUROG2 represses a subset but not all cell cycle regulators indicates that cell cycle exit is not an indirect consequence of neuronal differentiation but is precisely controlled by NEUROG2. Altogether our findings indicate that NEUROG2, by specifically repressing G1 and S cyclins, allows committed neuronal precursors to perform their last mitosis but blocks their re-entry in the cell cycle, thus favouring cell cycle exit.
Publication Title
NEUROG2 drives cell cycle exit of neuronal precursors by specifically repressing a subset of cyclins acting at the G1 and S phases of the cell cycle.
Sample Metadata Fields
Specimen part, Treatment
View Samples