This SuperSeries is composed of the SubSeries listed below.
Genome-wide profiling of methylation identifies novel targets with aberrant hypermethylation and reduced expression in low-risk myelodysplastic syndromes.
Specimen part
View SamplesSerum-dependent transcriptional networks identify distinct functional roles for H-ras and N-ras during initial stages of the cell cycle
No associated publication
Specimen part
View SamplesMesenchymal stromal cells (MSCs) derived from the BM of healthy donors (dMSCs) and myeloma patients (pMSCs) were co-cultured with the model myeloma cell line - MM.1S -, and the gene expression profile of MSCs induced by this interaction was analyzed using high density oligonucleotide microarrays. Deregulated genes in co-culture common to both d/pMSCs revealed functional involvement in tumor microenvironment cross-talk, myeloma growth induction and drug resistance, angiogenesis and signals for osteoclast activation and inhibition of osteoblasts. Additional genes induced by co-culture were exclusively deregulated in pMSCs and were predominantly associated to RNA processing, the ubiquitine-proteasome pathway, regulation of cell cycle and Wnt signaling.
Transcriptomic profile induced in bone marrow mesenchymal stromal cells after interaction with multiple myeloma cells: implications in myeloma progression and myeloma bone disease.
Specimen part
View SamplesGenome-wide expression and methylation profiling identifies novel targets with aberrant hypermethylation and reduced expression in low-risk myelodysplastic syndromes (MDSs).
Genome-wide profiling of methylation identifies novel targets with aberrant hypermethylation and reduced expression in low-risk myelodysplastic syndromes.
Specimen part
View SamplesBone 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.
A novel lung cancer signature mediates metastatic bone colonization by a dual mechanism.
No sample metadata fields
View SamplesWe used manual macrodissection or laser capture microdissection (LCM) to isolate tissue sections of the hippocampus area of Ras-GRF1 wild type and knockout mice brains, and analyzed their transcriptional patterns using commercial oligonucleotide microarrays. Comparison between the transcriptomes of macrodissected and microdissected samples showed that the LCM samples allowed detection of significantly higher numbers of differentially expressed genes, with higher statistical rates of significance. These results validate LCM as a reliable technique for in vivo genomic studies in the brain hippocampus, where contamination by surrounding areas (not expressing Ras-GRF1) increases background noise and impairs identification of differentially expressed genes. Comparison between wild type and knockout LCM hippocampus samples revealed that Ras-GRF1 elimination caused significant gene expression changes, mostly affecting signal transduction and related neural processes. The list of 36 most differentially expressed genes included loci concerned mainly with Ras/G protein signaling and cytoskeletal organization (i.e. 14-3-3/, Kcnj6, Clasp2) or related, cross-talking pathways (i.e. jag2, decorin, strap). Consistent with the phenotypes shown by Ras-GRF1 knockout mice, many of these differentially expressed genes play functional roles in processes such as sensory development and function (i.e. Sptlc1, antiquitin, jag2) and/or neurological development/neurodegeneration processes affecting memory and learning. Indeed, potential links to neurodegenerative diseases such as Alzheimer disease (AD) or Creutzfeldt-Jacobs disease (CJD), have been reported for a number of differentially expressed genes identified in this study (Ptma, Aebp2,Clasp2, Hebp1, 14-3-3/, Csnk1, etc.). These data, together with the previously described role of IRS and insulin (known Ras-GRF1 activators) in AD, warrant further investigation of a potential functional link of Ras-GRF1 to neurodegenerative processes.
Laser microdissection and microarray analysis of the hippocampus of Ras-GRF1 knockout mice reveals gene expression changes affecting signal transduction pathways related to memory and learning.
No sample metadata fields
View SamplesInsight into the role of Insulin-like Growth Factor (IGF) in development of lungs has come from the study of genetically modified mice. IGF1 is a key factor during lung development. IGF1 deficiency in the neonatal mouse causes respiratory failure collapsed alveoli and altered alveolar septa. To further characterize IGF1 function during lung development we analyzed Igf1-/- mouse prenatal lungs in a C57Bl/6 genetic background. Mutant lungs showed disproportional hypoplasia, disorganized extracellular matrix and dilated alveolar capillaries. IGF1 target genes during lung maturation were identified by analyzing RNA differential expression in Igf1-/- lungs using microarrays.
Transcriptome analysis in prenatal IGF1-deficient mice identifies molecular pathways and target genes involved in distal lung differentiation.
Specimen part
View SamplesCystatin D (CST5) is an inhibitor of several proteases of the cathepsin family that inhibits cell proliferation, migration and invasion of colon carcinoma cells. Some of these effects are unrelated to its antiprotease activity. Here, we use genome-wide expression microarrays to show that cystatin D regulates gene expression (including that of genes encoding transcription factors such as RUNX1, RUNX2, or MEF2C) in HCT116 cells.
Cystatin D locates in the nucleus at sites of active transcription and modulates gene and protein expression.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genomic characterization of liver metastases from colorectal cancer patients.
Sex, Age, Disease, Disease stage
View SamplesBackground: Even though much progress has been made in the understanding of the molecular nature of glioma, the survival rates of patients affected of this tumour have not changed significantly during these years. Thus, a deeper understanding of this malignancy is still needed in order to predict its outcome and improve patient treatment. Here, we report that VAV1, a GDP/GTP exchange factor for Rho/Rac proteins with oncogenic potential that is involved in the regulation of cytoskeletal dynamics and cell migration.
No associated publication
Sex, Age
View Samples