Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA147051 | ENA |
REPOSITORIES: ENA
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Project description:Naturally occurring genetic polymorphisms influence patterns of gene expression in normal tissues, and can provide a molecular view of the component cell lineages and signaling pathways responsible for normal tissue architecture. Analysis of the coordinated changes in this architecture that take place during tumor development can help to identify the functional roles of oncogenes or tumor suppressors and provide potential new therapeutic targets. We have applied a network analysis approach to a set of 92 normal human lung samples from cancer patients and their matched adenocarcinomas. We have identified networks associated with particular cell lineages (alveolar type 2 pneumocytes and Clara cells) in normal lung and document the changes in these networks that accompany transformation to adenocarcinomas. Expression of the transcription factor NKX2-1 (TTF1) is linked to surfactant protein markers of the alveolar type 2 lineage in normal and transformed lung cells, but its network is rewired in tumors to include pathways linked to cell growth such as glutaminase (GLS2). Analysis of mitotic networks revealed the presence of novel components such as the kinase VRK1 that are preferentially linked to the mitotic cycle in tumors but not in normal lung. We show that shRNA-mediated inhibition of VRK1 cooperates with inhibition of PARP signaling to inhibit growth of lung tumor cells. Targeting of genes that are recruited into tumor mitotic networks may provide a wider therapeutic window than that seen by inhibition of integral components of the mitotic machinery such as Aurora kinases. 87 lung adenocarcinomas and 92 adjacent uninvolved lung tissue samples, 85 matched pairs
2013-04-01 | E-GEOD-32665 | biostudies-arrayexpress
Project description:Naturally occurring genetic polymorphisms influence patterns of gene expression in normal tissues, and can provide a molecular view of the component cell lineages and signaling pathways responsible for normal tissue architecture. Analysis of the coordinated changes in this architecture that take place during tumor development can help to identify the functional roles of oncogenes or tumor suppressors and provide potential new therapeutic targets. We have applied a network analysis approach to a set of 92 normal human lung samples from cancer patients and their matched adenocarcinomas. We have identified networks associated with particular cell lineages (alveolar type 2 pneumocytes and Clara cells) in normal lung and document the changes in these networks that accompany transformation to adenocarcinomas. Expression of the transcription factor NKX2-1 (TTF1) is linked to surfactant protein markers of the alveolar type 2 lineage in normal and transformed lung cells, but its network is rewired in tumors to include pathways linked to cell growth such as glutaminase (GLS2). Analysis of mitotic networks revealed the presence of novel components such as the kinase VRK1 that are preferentially linked to the mitotic cycle in tumors but not in normal lung. We show that shRNA-mediated inhibition of VRK1 cooperates with inhibition of PARP signaling to inhibit growth of lung tumor cells. Targeting of genes that are recruited into tumor mitotic networks may provide a wider therapeutic window than that seen by inhibition of integral components of the mitotic machinery such as Aurora kinases.
2013-04-01 | GSE32665 | GEO
Project description:Human Lung Adenocarcinomas (Stage 1 and Stage 2 )
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Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
2010-09-25 | GSE24338 | GEO
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
2011-02-19 | GSE20463 | GEO
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO
Project description:Gene methylation profiling of immortalized human mesenchymal stem cells comparing HPV E6/E7-transfected MSCs cells with human telomerase reverse transcriptase (hTERT)- and HPV E6/E7-transfected MSCs. hTERT may increase gene methylation in MSCs. Goal was to determine the effects of different transfected genes on global gene methylation in MSCs.
2011-08-25 | GSE23936 | GEO
Project description:Copy number variations distinguish lung adenocarcinomas from squamous cell carcinomas
| PRJNA301991 | ENA