The behavior of breast cancers and their response to different chemotherapy treatments depend on their phenotype which is to a large extent determined by gene expression programs within the cancer cell.
Evaluation of a 30-gene paclitaxel, fluorouracil, doxorubicin, and cyclophosphamide chemotherapy response predictor in a multicenter randomized trial in breast cancer.
Age, Race
View SamplesDeregulated expression of the Myc transcription factor is a frequent causal mutation in human cancer. Thousands of putative Myc target genes have been identified in in vitro studies, indicating that Myc exerts highly pleiotropic effects within cells and tissues. However, the complexity and diversity of Myc gene targets has confounded attempts at identifying which of these genes are the critical targets mediating Myc-driven tumorigenesis in vivo. Acute activation of Myc in a reversibly switchable transgenic model of Myc-mediated cell tumorigenesis induces rapid tumor onset whereas subsequent Myc de-activation triggers equally rapid tumor regression. Thus, sustained Myc activity is required for tumor maintenance. We have used this reversibly switchable kinetic tumor model in combination with high-density oligonucleotide microarrays to develop an unbiased strategy for identifying candidate Myc-regulated genes responsible for maintenance of Myc-dependent tumors. Consistent with known Myc functions, some Myc-regulated genes are involved in cell growth, cycle and proliferation. In addition, however, many Myc-regulated genes are specific to cells, indicating that a significant component of Myc action is cell-type specific. Finally, we identify a very restricted cadre of genes whose expression is inversely regulated upon Myc activation-induced tumor progression and de-activation-induced tumor regression. By definition, such genes are candidates for tumor maintenance functions. Combining reversibly switchable, transgenic models of tumor formation and regression with genomic profiling offers a novel strategy with which to deconvolute the complexities of oncogenic signaling pathways in vivo
Reversible kinetic analysis of Myc targets in vivo provides novel insights into Myc-mediated tumorigenesis.
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A genomic predictor of response and survival following taxane-anthracycline chemotherapy for invasive breast cancer.
Specimen part, Disease stage
View SamplesPURPOSE: To develop a predictive test for response and survival following neoadjuvant taxane-anthracycline chemotherapy for HER2-negative invasive breast cancer.
A genomic predictor of response and survival following taxane-anthracycline chemotherapy for invasive breast cancer.
Specimen part, Disease stage
View SamplesPURPOSE: To develop a predictive test for response and survival following neoadjuvant taxane-anthracycline chemotherapy for HER2-negative invasive breast cancer.
A genomic predictor of response and survival following taxane-anthracycline chemotherapy for invasive breast cancer.
Specimen part, Disease stage
View SamplesZnf536 mutant and wild types were profiled to discover cell type landscape modulated by the transcription factor. Overall design: 10x libraries of single cell transcriptomes
Phenotypic Landscape of Schizophrenia-Associated Genes Defines Candidates and Their Shared Functions.
Specimen part, Subject
View SamplesThe overall aim of this experiment was to identify specific genes and molecular pathways regulated by ML290, a small molecule agonist of the relaxin receptor, RXFP1, in the context of liver fibrosis. Overall design: Whole transcriptome mRNA sequencing of transformed LX-2 cells using HiSeq platforms with paired-end 150 bp (PE 150) sequencing strategy, with four biological replicates in each treatment group.
Therapeutic effects of a small molecule agonist of the relaxin receptor ML290 in liver fibrosis.
Specimen part, Cell line, Subject
View SamplesOne of the major players controlling RNA decay is the cytoplasmic 5'-to-3' exoribonuclease, which is conserved among eukaryotic organisms. In Arabidopsis, the 5'-to-3' exoribonuclease XRN4 is involved in disease resistance, the response to ethylene, RNAi, and miRNA-mediated RNA decay. Curiously, XRN4 appears to display selectivity among its substrates because certain 3' cleavage products formed by miRNA-mediated decay, such as from ARF10 mRNA, accumulate in the xrn4 mutant, whereas others, such as from AGO1, do not. To examine the nature of this selectivity, transcripts that differentially accumulate in xrn4 were identified by combining PARE and Affymetrix arrays. Certain functional categories, such as stamen-associated proteins and hydrolases, were over-represented among transcripts decreased in xrn4, whereas transcripts encoding nuclear-encoded chloroplast-targeted proteins and nucleic acid-binding proteins were over-represented in transcripts increased in xrn4. To ascertain if RNA sequence influences the apparent XRN4 selectivity, a series of chimeric constructs was generated in which the miRNA-complementary sites and different portions of the surrounding sequences from AGO1 and ARF10 were interchanged. Analysis of the resulting transgenic plants revealed that the presence of a 150 nucleotide sequence downstream from the ARF10 miRNA-complementary site conferred strong accumulation of the 3' cleavage products in xrn4. In addition, sequence analysis of differentially accumulating transcripts led to the identification of 27 hexamer motifs that were over-represented in transcripts or miRNA-cleavage products accumulating in xrn4. Taken together, the data indicate that specific mRNA sequences, like those in ARF10, and mRNAs from select functional categories are attractive targets for XRN4-mediated decay.
Evidence that XRN4, an Arabidopsis homolog of exoribonuclease XRN1, preferentially impacts transcripts with certain sequences or in particular functional categories.
Specimen part
View SamplesCertain neuron types fire spontaneously at high rates, an ability that is crucial for their function in brain circuits. The spontaneously active GABAergic neurons of the substantia nigra pars reticulata (SNr), a major output of the basal ganglia, provide tonic inhibition of downstream brain areas. A depolarizing "leak" current supports this firing pattern, but its molecular basis remains poorly understood. To understand how SNr neurons maintain tonic activity, we used single-cell RNA sequencing to determine the transcriptome of individual SNr neurons. We discovered that SNr neurons express the sodium leak current, NaLCN and that SNr neurons lacking NaLCN have impaired spontaneous firing. Overall design: RNA sequencing profiles from 87 GFP-positive GABAergic SNr neurons and 9 GFP-negative SNr cells were carried out. However only 80 samples that passed initial quality control and that were included in the data processing are represented in this record.
The leak channel NALCN controls tonic firing and glycolytic sensitivity of substantia nigra pars reticulata neurons.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of artifactual microarray probe signals constantly present in multiple sample types.
Specimen part
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