Transcription profiling of a mouse transgenic that targets expression of an oncogenic Met receptor reveals Met induces mammary tumors with diverse histologies and is associated with poor outcome and human basal breast cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Robert Lesurf
PROVIDER: E-GEOD-10450 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Shared Molecules
Only show the datasets with similarity scores above: 0.5
Threshold
0.5
Similar Datasets
Project description:Overexpression and/or amplification of the ErbB-2 oncogene, as well as inactivation of the tumor suppressor PTEN, are two important genetic events in human breast carcinogenesis. To address the biological impact of conditional inactivation of PTEN on ErbB-2-induced mammary tumorigenesis, we generated a novel transgenic mouse model that utilizes the MMTV promoter to directly couple expression of activated ErbB-2 and Cre recombinase to the same mammary epithelial cell (MMTV-NIC). Disruption of PTEN in the mammary epithelium of the MMTV-NIC model system dramatically accelerated the formation of multifocal and highly metastatic mammary tumors, which exhibit homogenous pathology. PTEN-deficient/NIC tumorigenesis was associated with an increase in angiogenesis. Moreover, inactivation of PTEN in the MMTV-NIC mouse model resulted in hyperactivation of the PI3K/Akt signalling pathway. However, like the parental strain, tumors obtained from PTEN-deficient/NIC mice displayed histopathological and molecular features of the luminal-like subtype of breast cancer. Taken together, our findings provide important implications in understanding the molecular determinants of mammary tumorigenesis driven by PTEN deficiency and ErbB-2 activation, and could provide a valuable tool for testing the efficacy of therapeutic strategies that target these critical signalling pathways. Experiment Overall Design: Common reference design. 9 samples (including 2 normal tissue and 7 tumor tissue samples) replicated twice as dye swaps, generating a total of 18 arrays.
2009-07-03 | E-GEOD-13916 | biostudies-arrayexpress
Project description:Although ERBB2 amplification and overexpression is correlated with poor outcome in breast cancer, the molecular mechanisms underlying the aggressive nature of these tumors has not been fully elucidated. To investigate this further, we have used a transgenic mouse model of ErbB2-driven tumor progression (ErbB2KI model) that recapitulates clinically relevant events, including selective amplification of the core erbB2 amplicon. By comparing the transcriptional profiles of ErbB2KI mammary tumors and human ERBB2-positive breast cancers, we demonstrate that ErbB2KI tumors possess molecular features of the basal subtype of ERBB2-positive human breast cancer, including activation of canonical β-catenin signaling. Inhibition of β-catenin-dependent signaling in ErbB2KI-derived tumor cells using RNA interference impaired tumor initiation and metastasis. Furthermore, treatment of ErbB2KI or human ERBB2-overexpressing tumor cells with a selective β-catenin/CBP inhibitor significantly decreased proliferation and ErbB2 expression. Collectively, our data indicate that ERBB2-mediated breast cancer progression requires β-catenin signaling and can be therapeutically targeted by selective β-catenin/CBP inhibitors. Common reference design. 9 samples (including 2 normal tissue, 2 NIC tumors, and 5 KI tumor tissue samples) replicated twice as dye swaps, generating a total of 18 arrays.
2013-06-02 | E-GEOD-37954 | biostudies-arrayexpress
Project description:Children less than 2 years of age are capable of healing large calvarial defects, whereas adults have been found to lack this endogenous ability. In this study, we used microarray analysis to compare genomewide expression patterns during active regeneration after injury with calvaria in skeletally immature and mature mice. Parietal bone defects were created in 6-day-old (juvenile) and 60-day-old (adult) mice using a 4-mm trephine bit (n = 20 mice per age group). The calvarial disc was removed, leaving the underlying dura mater intact. Two weeks after injury, the region of regeneration with the underlying dura mater was harvested, and RNA was extracted for microarray analysis. The 25 most differentially upregulated genes in juvenile regenerates compared with adults were listed, as well as selected bone-related genes. In addition, QRT-PCR confirmation of specific genes was performed for validation. Juvenile regenerates expressed significantly greater amounts of BMP-2, -4, -7, as well as FGF-2 and its receptor FGFR-1. Various other growth factors were also noted to be upregulated, including IGF-2 and Ptn. This corresponded with the increased expression of markers for osteogenic differentiation of Sparc and Oc. Markers of osteoclast activity, Acp5, Ctsk, and Mmp2, were noted to be greater in juvenile regenerates compared with adults. The observation of Mmp14 upregulation, however, highlights the importance of balanced osteoclast-mediated bone resorption for ultimate healing. The 2 most differentially regulated genes, transthyretin (Ttr) and prostaglandin D2 synthase (Ptgds), highlight the potential role of retinoic acid signaling and the prostaglandin axis on skeletal regeneration. These findings underscore the multitude of biomolecular mechanisms at play, allowing juvenile calvaria to heal after injury. The identification of various growth factors and cytokines involved also suggests novel therapeutic strategies for tissue-engineering purposes. Set of arrays that are part of repeated experiments Elapsed Time: Calvarial regeneration in 6 day old vs 60 day old mice Biological Replicate
2009-01-14 | E-GEOD-14424 | biostudies-arrayexpress
Project description:The innate immune system responds to unique molecular signatures that are widely conserved among microbes but that are not normally present in host cells. Compounds that stimulate innate immune pathways may be valuable in the design of novel adjuvants, vaccines, and other immunotherapeutics.The cyclic dinucleotide cyclic-di-guanosine monophosphate (c-di-GMP) is a recently appreciated second messenger that plays critical regulatory roles in many species of bacteria but is not produced by eukaryotic cells. In vivo and in vitro studies have previously suggested that c-di-GMP is a potent immunostimulatory compound recognized by mouse and human cells. Here we provide evidence that c-di-GMP is sensed in the cytosol of mammalian cells via a novel immunosurveillance pathway. The potency of cytosolic signaling induced by cyclic-di- GMP is comparable to that induced by cytosolic delivery of DNA, and both nucleic acids induce a similar transcriptional profile, including triggering of type I interferons and coregulated genes via induction of TBK1, IRF3, NF-!B and MAP kinases. However, the cytosolic pathway that senses c-di-GMP appears to be distinct from all known nucleic acid-sensing pathways.Our results suggest a novel mechanism by which host cells can induce an inflammatory response to a widely produced bacterial ligand. Three-condition experiment: macrophages transfected with mono-GMP (negative control), double-stranded DNA (positive control), or cyclic-di-GMP (experimental condition). Biological replicates: two, independently treated, harvested, and hybridized to arrays. One replicate per array, except two technical replicates were performed for one of the positive control samples.
2009-07-21 | E-GEOD-16943 | biostudies-arrayexpress
Project description:Co-hybridization of Adenovirus type 40 and 41 to test probe specificity for closely related viral targets. ATCC strains of Adenovirus type 40 and 41 were hybridized to the array as a control run and a proof of concept. Degree of cross hybridization between polio nucleic acid and non-adenovirus 40 and 41 probes was evaluated. Specificity of the probe design was determined between closely related members of the same virus family. Keywords: control study: target detection and specificity 2 lab strains of adenovirus (type 40 and 41) were extracted directly from ATCC samples. Viral DNA was was extracted and labeled with Cy3 and Cy5 dyes for Adenovirus type 40 and 41 respectively.
2010-05-26 | E-GEOD-10569 | biostudies-arrayexpress
Project description:SLE patients are always with various disease manifestation. Various cytokines are pointed interacting and playing pathological roles in SLE although the etiopathology is still obscure. In this study, we aimed to investigate the effects of cytokine interactions in the immune response of SLE patients. Overexpressed interferon-inducible(IFI) genes were confirmed in peripheral blood from SLE patients. Using network-based analysis on the immune response-related genes, several networks including cytokines such as TNF and IFN-γ, or beta-estradiol(E2), were constructed. TNF-regulated genes were dominant in these networks but in vitro TNF stimulation on PBMCs showed no different responses in the expressions of these genes between SLE and healthy individuals. Co-stimulating experiments by TNF, IFN-γ, and E2 with IFN-α, revealed that TNF has repressive while IFN-γ essentially has synergistic effect with IFN-α on IFI gene expressions in vitro. E2 showed different effects on IFI gene expressions among 3 individuals. Peripheral blood was obtained from patients with SLE (n=11) and healthy women (n=6). Gene expression profile was analyzed using DNA microarray covering 30,000 human genes. Differentially expressed immune response-related genes were selected and analyzed by using Expression Analysis Systemic Explorer (EASE) based on Gene Ontology (GO) followed by network pathway analysis with Ingenuity Pathways Analysis (IPA).
2009-05-31 | E-GEOD-12374 | biostudies-arrayexpress
Project description:The aim of the present study was to compare, on a statistical basis, the performance of different microarray platforms to detect differences in gene expression in a realistic and challenging biological setting. Gene expression profiles in the hippocampus of five wild-type and five transgenic δC-doublecortin-like kinase mice were evaluated with five microarray platforms: Applied Biosystems, Affymetrix, Agilent, Illumina and home-spotted oligonucleotide arrays. We observed considerable overlap between the different platforms, the overlap being better detectable with significance level-based ranking than with a p-value based cut-off. Confirming the qualitative agreement between platforms, Pathway analysis consistently demonstrated aberrances in GABA-ergic signalling in the transgenic mice, even though pathways were represented by only partially overlapping genes on the different platforms. Keywords: microarray platform comparison 5 biological replicates for each experimental group were analyzed on each of the five platforms. For two-color arrays a dye swap was performed. ABI_raw_data.csv contains the raw data for GSM206638 to GSM206647. Illumina_raw_data.csv contains the raw data for GSM206887 to GSM206896. In these files, the sample identifiers are included in the column headers.
2010-06-25 | E-GEOD-8349 | biostudies-arrayexpress
Project description:Systemic-onset juvenile idiopathic arthritis (soJIA) is a rheumatic disease in childhood characterized by systemic symptoms and a relatively poor prognosis. The peripheral leukocytes are thought to play the pathological role of soJIA although the exact cause is still obscure. In this study, we aimed to clarify the cellular functional abnormality in those cells. Here, we analyzed the gene expression profile in peripheral leukocytes from 51 patients with soJIA, 6 patients with poly-articular type JIA (polyJIA) and 8 healthy children utilizing DNA microarrays. A total of 3,491 genes, including genes related to immune reponse and metabolism, were differentially expressed in patients with soJIA compared to healthy individuals. The result provides insight into the pathogenesis of soJIA. Keywords: disease state analysis Total RNA was extracted from peripheral leukocytes from 51 soJIA patients, 6 poly-articular type JIA patients, and 8 healthy children. The gene expression profile was analyzed with DNA microarrays.
2010-05-26 | E-GEOD-8361 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE10873: Ozone exposure of tolerant and sensitive F2 genotypes of Populus GSE10874: Ozone exposure of Populus deltoides and Populus trichocarpa Keywords: SuperSeries Refer to individual Series
2009-04-01 | E-GEOD-10932 | biostudies-arrayexpress
Project description:The unsurpassed simplicity of the fruitflyâs airway epithelium, that is made of homogenous epithelial cells only, favours its use as a model to study general features and response characteristics of airway epithelia in general. All epithelial cells are able to launch an immune response as characterized by the expression of antimicrobial peptide genes. Infection induces a complex change in the expression profile of these epithelial cells. Outstanding are a priming of the immune system and the launch of a survival program, presumably to counteract infection induced apoptotic signals, which comprises the concurrent expression of known longevity genes such as dFoxo, and dThor. In regions of the airway epithelium with strong immune reactions, a complex remodelling of the airways can be observed, which is characterized by metaplasia and presumably also by hyperplasia of the affected epithelial cells. At the transcriptional level, this reorganization of the airway epithelium is mirrored by a recapitulation of genetic programs that are characteristic for early phases of airway development. Taken together, the response characteristics of the flyâs airway epithelium towards infections discloses features that are known from inflammatory diseases of the human lung, thus opening the opportunity to study fundamental aspects of these diseases in the fly. Keywords:infection, Erwinia c., third instar larva, airway epithelium, two-colour microarray Infection of the airway epithelium by the gram-negativ bacteria Erwinia carotovora. For the infection experiments third instar larvae of the GFP-reporter strain YW DD1 were used and only isolated when the whole epithelium of the airway epithelium showed GFP expression. Uninfected larvae were used as controls. In general, four replicates were performed including dye-swaps. A table of significantly-regulated genes from the SAM-output and GeneTraffic-output has been linked as a supplementary file at the foot of this record.
2010-05-19 | E-GEOD-11444 | biostudies-arrayexpress