For this study we selected a gene, -synuclein (SNCA), that is consistently under-expressed in MCF7 cells and breast tumors. Following transfection with an SNCA expression construct, two stable MCF7 clones (named MCF7-SNCA #1 and 2) were selected and examined for expression differences relative to the parental MCF7 cells.
Cancer develops, progresses and responds to therapies through restricted perturbation of the protein-protein interaction network.
Specimen part, Cell line
View SamplesAberrant cell signaling can cause cancer and other diseases and is a focal point of drug research. A common approach is to infer signaling activity of pathways from gene expression. However, mapping gene expression to pathway components disregards the effect of post-translational modifications, and downstream signatures represent very specific experimental conditions. Here we present PROGENy, a method that overcomes both limitations by leveraging a large compendium of publicly available perturbation experiments to yield a common core of Pathway RespOnsive GENes. Unlike existing methods, PROGENy can (i) recover the effect of known driver mutations, (ii) provide or improve strong markers for drug indications, and (iii) distinguish between oncogenic and tumor suppressor pathways for patient survival. Collectively, these results show that PROGENy accurately infers pathway activity from gene expression. Overall design: HEK293?RAF1:ER cells were treated with different stimuli (4OHT, Ly29002, TNFa, TGF1b, IFNg) for different periods of time (1h, 4h).
Perturbation-response genes reveal signaling footprints in cancer gene expression.
Specimen part, Subject
View SamplesBased on the results of numerous clinical and preclinical analyses, the transcription factor HIF-1a has been identified as an important tumor-promoting factor and is considered to be an attractive target for cancer therapy. To further deconstruct the molecular nature of HIF-1as role in tumorigenesis, we have applied lentiviral shRNA transduction to establish HIF-1a-deficient gastric cancer cells. Interestingly, functional analyses failed to show a significant growth defect of HIF-1a-deficient gastric cancer cells in vitro and in vivo. These observations led us to propose that stable inactivation of HIF-1a resulted in efficient compensation enabling cell growth and, ultimately, tumor progression in a HIF-1a-independent manner. To better understand the mechanisms that control this compensation, we performed transcriptomics of control (scrambled (SCR)) and HIF-1a-deficient (HIF) gastric cancer cells.
Annexin A1 sustains tumor metabolism and cellular proliferation upon stable loss of HIF1A.
Specimen part, Cell line
View SamplesReproducibility in research can be compromised by both biological and technical variation, but most of the focus is on removing the latter. Here we investigate the effects of biological variation in HeLa cell lines using a systems-wide approach. We determine the degree of molecular and phenotypic variability across 14 stock HeLa samples from 13 international laboratories. We cultured cells in uniform conditions and profiled genome-wide copy numbers, mRNAs, proteins and protein turnover rates in each cell line. We discovered substantial heterogeneity between HeLa variants, especially between lines of the CCL2 and Kyoto varieties, and observed progressive divergence within a specific cell line over 50 successive passages. Genomic variability has a complex, nonlinear effect on transcriptome, proteome and protein turnover profiles, and proteotype patterns explain the varying phenotypic response of different cell lines to Salmonella infection. These findings have implications for the interpretation and reproducibility of research results obtained from human cultured cells. Overall design: Multi-omic (genome, transcriptome, proteome, protein turnover) analysis of 14 HeLa cell lines obtained from different laboratories but grown under the same conditions.
Multi-omic measurements of heterogeneity in HeLa cells across laboratories.
Specimen part, Subject
View SamplesComparison of the transcriptome of human kideny cancer cells either wild-type for FH or FH-deficient. The UOK262 cells were isolated from mediastinum metastasis of a HLRCC patient (Yang et al. Cancer Genetics and Cytogenetics, Volume 196, Issue 1, 1 January 2010, Pages 45–55). FH function was restored in the UOK262 by re-expressing the FH transcript from an exogenous plasmid. Overall design: Examination of gene transciption in 2 cell types.
Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition.
No sample metadata fields
View SamplesComparison of the transcriptome of immortalised mouse kidney epithelial cells either wt for Fh1 or Fh1-deficient. The cells were isolated from kidneys of P5 mouse(see Frezza et al, Nature 2011). Briefly, Fh1_fl (flox) are wt for Fh1 (floxed cassette not excised), clone 1 and clone 19 are two different Fh1-deificent clones (floxed cassette excised) and Rec are clone 19 with reconstituted Fh1 expression from exogenous plasmid. Overall design: Examination of gene transciption in 4 cell types.
Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition.
Specimen part, Cell line, Subject
View SamplesAnalysis of Diffuse Large B-Cell Lymphoma (DLBCL) OCI-LY3 cell line treated with 14 different known drugs at 2 different concentrations and profiled at 6, 12 and 24 hrs after treatment.
A community computational challenge to predict the activity of pairs of compounds.
Compound, Time
View SamplesIn Rspondin-based 3D cultures, Lgr5 stem cells from multiple organs form ever-expanding epithelial organoids that retain their tissue identity. We report the establishment of tumor organoid cultures from 20 consecutive colorectal (CRC) patients. For most, organoids were also generated from adjacent normal tissue. The organoids closely resemble the original tumor. The spectrum of genetic changes observed within the 'living biobank' agrees well with previous large-scale mutational analyses of CRC. Gene expression analysis indicates that the major CRC molecular subtypes are represented. Tumor organoids are amenable to robotized, high-throughput drug screens allowing detection of gene-drug associations. As an example, a single organoid culture was exquisitely sensitive to Wnt secretion (porcupine) inhibitors and carried a mutation in the negative Wnt feedback regulator RNF43 (rather than in APC). Organoid technology may fill the gap between cancer genetics and patient trials, complement cell line- and xenograft-based drug studies and allow personalized therapy design.
Prospective derivation of a living organoid biobank of colorectal cancer patients.
Specimen part, Disease, Disease stage, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integration of light and temperature in the regulation of circadian gene expression in Drosophila.
No sample metadata fields
View SamplesCircadian clocks are temporally aligned to the environment via signals, or Zeitgebers, such as daily light and temperature cycles, food availability, and social behavior. In this study, we show that genome-wide expression profiles from temperature-entrained flies show a dramatic difference in the presence or absence of a thermocycle. Whereas transcription appears to be modified globally by changes in temperature, there is a specific set of transcripts that continue to oscillate in constant conditions following temperature entrainment. These transcripts show a significant overlap with a previously defined set of transcripts oscillating in response to a photocycle. Further, these overlapping transcripts maintain the same mutual phase relationships after entrainment by temperature or light. Comparison of the collective temperature- and light-entrained circadian phases indicates that natural environmental light and temperature cycles cooperatively entrain the circadian clock. These findings suggest that a single transcriptional clock in the adult fly head is able to integrate information from both light and temperature.
Integration of light and temperature in the regulation of circadian gene expression in Drosophila.
No sample metadata fields
View Samples