We tested the gene expression difference between PDGFRa+ fibroblasts FACS sorted from nulliparous balb/c mouse mammary glands and 6 days post-weaning mammary glands Overall design: 2 biological replicates of fibroblasts from nulliparous mammary glands and 3 biological replicates of fibroblasts from 6 days post-weaning mammary glands were used for comparison.
Physiologically activated mammary fibroblasts promote postpartum mammary cancer.
Specimen part, Cell line, Subject
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Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB.
Cell line
View SamplesTo gain global insights into the role of the well-known repressive splicing regulator PTB we analyzed the consequences of PTB knockdown in HeLa cells using high-density oliogonucleotide splice-sensitive microarrays. The major class of identified PTB-regulated splicing event was PTB-repressed cassette exons, but there was also a substantial number of PTB-activated splicing events. PTB repressed and activated exons showed a distinct arrangement of motifs with pyrimidine-rich motif enrichment within and upstream of repressed exons, but downstream of activated exons. The N-terminal half of PTB was sufficient to activate splicing when recruited downstream of a PTB-activated exon. Moreover, insertion of an upstream pyrimidine tract was sufficient to convert a PTBactivated to a PTB-repressed exon. Our results demonstrate that PTB, an archetypal splicing repressor, has variable splicing activity that predictably depends upon its binding location with respect to target exons.
Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Comparative analyses of gene copy number and mRNA expression in glioblastoma multiforme tumors and xenografts.
Specimen part, Disease stage
View SamplesDevelopment of model systems that recapitulate the molecular heterogeneity observed amongst GBM tumors will expedite the testing of targeted molecular therapeutic strategies for GBM treatment. In this study, we profiled DNA copy number and mRNA expression in 21 independent GBM tumor lines maintained as subcutaneous xenografts (GBMX), and compared GBMX molecular signatures to those observed in GBM clinical specimens derived from The Cancer Genome Atlas (TCGA). The predominant copy number signature in both tumor groups was defined by chromosome-7-gain/chromosome-10-loss, a poor prognosis genetic signature. We also observed, at frequencies similar to that detected in TCGA GBMs genomic amplification and overexpression of known GBM oncogenes such as EGFR, MDM2, CDK6 and MYCN, and novel genes including NUP107, SLC35E3, MMP1, MMP13 and DDX1. The transcriptional signature of GBMX tumors, which was stable over multiple subcutaneous passages, was defined by overexpression of genes involved in M-phase, DNA Replication, and Chromosome organization (MRC) and was highly similar to the poor-prognosis mitosis-and-cell-cycle-module (MCM) in GBM. Assessment of gene expression in TCGA-derived GBMs revealed overexpression of MRC cancer genes AURKB, BIRC5, CCNB1, CCNB2, CDC2, CDK2, and FOXM1, which form a transcriptional network important for G2/M- progression and/or -checkpoint activation. In conclusion, our study supports propagation of GBM tumors as subcutaneous xenografts as a useful approach for sustaining key molecular characteristics of patient tumors, and highlights therapeutic opportunities conferred by this GBMX tumor panel for testing targeted therapeutic strategies for GBM treatment.
Comparative analyses of gene copy number and mRNA expression in glioblastoma multiforme tumors and xenografts.
Specimen part, Disease stage
View SamplesPancreatic ductal adenocarcinoma (PDA) carries a dismal prognosis and current treatments are only modestly effective. We present evidence that this variation is caused in part by recurrent, pervasive molecular differences between tumors. mRNA expression profiles measured using microdissected PDA clinical samples reveal three dominant subtypes of disease; epithelial, mesenchymal and acinar-like. The classical and quasi-mesenchymal subtypes are observed in human and mouse PDA cell lines. Importantly, responses to cytotoxics and KRAS depletion in human PDA cell lines differ substantially between subtypes, and in opposing directions. Integrated genomics implicate and functional studies support overexpression of the trancription factor GATA6 as a driver of the epithelial subtype. These results provide a molecular framework for evaluating the prospects of personalized treatment in PDA.
Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy.
Specimen part, Cell line
View SamplesRecent studies suggest that thousands of genes may contribute to breast cancer pathophysiologies when deregulated by genomic or epigenomic events. Here, we describe a model system to appraise the functional contributions of these genes to breast cancer subsets. In general, the recurrent genomic and transcriptional characteristics of 51 breast cancer cell lines mirror those of 145 primary breast tumors, although some significant differences are documented. The cell lines that comprise the system also exhibit the substantial genomic, transcriptional, and biological heterogeneity found in primary tumors. We show, using Trastuzumab (Herceptin) monotherapy as an example, that the system can be used to identify molecular features that predict or indicate response to targeted therapies or other physiological perturbations.
A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes.
Cell line
View SamplesAssessment of chemo- and radiation therapy-naïve biopsy-confirmed invasive human breast tumors by RNAseq. Overall design: 103 total samples from 63 unique patients. Clinical details were provided only for the 50 samples in current publication. However, all 103 samples were analyzed together.
Human Tumor-Associated Macrophage and Monocyte Transcriptional Landscapes Reveal Cancer-Specific Reprogramming, Biomarkers, and Therapeutic Targets.
Age, Specimen part, Disease stage, Subject
View Samples56 breast cancer cell lines were profiled to identify patterns of gene expression associated with subtype and response to therapeutic compounds. Overall design: Cell lines were profiled in their baseline, unperturbed state.
Modeling precision treatment of breast cancer.
No sample metadata fields
View SamplesWe used microarrays to detail the global gene expression changes following apical infection of porcine choroid plexus epithelial cells (PCPEC) with Streptococcus suis (S. suis)
In vitro transcriptome analysis of porcine choroid plexus epithelial cells in response to Streptococcus suis: release of pro-inflammatory cytokines and chemokines.
Specimen part
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