Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Translational profiling shows aberrant translational regulation in primary mesothelioma cells compared to untransformed mesothelium control cells

ABSTRACT: Malignant mesothelioma (MpM) is an aggressive, fatal tumour, associated with asbestos exposure, for which there is no curative therapy and the mechanism of carcinogenesis is poorly understood. We use translational profiling to show that dysregulated post-transcriptional control makes a major contribution to aberrant cell growth in primary MpM cells, with elevated signalling through the mTOR axis activating mRNA translation initiation.

INSTRUMENT(S): Agilent SureScan High Resolution scanner

ORGANISM(S): Homo sapiens

SUBMITTER: Stefano Grosso

PROVIDER: E-MTAB-8167 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Background: In classrooms high concentrations of particulate matter PM10 were measured. It is unknown whether the hazard of indoor particles is similar to that of the better studied outdoor particles. This study therefore analyzed adverse biological effects of classroom in comparison to outdoor PM10. Methods: Samples were taken from six schools during teaching hours. Genome-wide gene expression in human bronchial BEAS-2B epithelial cells was analyzed, and regulated genes were verified by quantitative PCR. Polycyclic aromatic hydrocarbons (PAH), endotoxin, and cat allergen Fel d 1 were analyzed with standard methods. Enhancement of allergic reactivity by PM10 was confirmed with CD63 upregulation in human primary basophils. Acceleration of human blood coagulation was determined with supernatants of PM10-exposed human peripheral blood monocytes. Results: Indoor PM10 induced SERPINB2 (involved in blood coagulation) and inflammatory genes (like CXCL6, CXCL1, IL6, IL8, all p<0.001). Outdoor PM10 induced xenobiotic metabolizing enzymes (CYP1A1, CYP1B1, TIPARP, all p<0.001). The induction of inflammatory genes by indoor PM10 could be explained by endotoxin (indoor 128.5M-BM-142.2EU/mg versus outdoor 13.4M-BM-121.5EU/mg, p<0.001), the induction of CYP by outdoor PAH (indoor 8.3M-BM-14.9ng/mg versus outdoor 16.7M-BM-115.2ng/mg, p<0.01). The induction of SERPINB2 was confirmed by a more rapid human blood coagulation (p<0.05). Indoor PM10 had no effect on the allergic reactivity from human primary basophils, except in cat allergic individuals. This was explained by varying Fel d 1 concentrations in indoor PM10 (p<0.001). Conclusions: Indoor PM10, compared to outdoor PM10, was 6 times higher, had a different composition, and on an equal weight basis induced more inflammatory and allergenic reactions, and accelerated blood coagulation. Outdoor PM10 had significantly lower effects, but induced detoxifying enzymes. Therefore, preliminary interventions for the reduction of classroom PM10 seem reasonable, perhaps by intensified ventilation. For genome-wide gene expression analysis, BEAS-2B cells (passage 41) were incubated with 10M-BM-5g/ml PM10 (school 4 indoor and outdoor) for 4, 10 or 24h, all in triplicate. experiment type : time course

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Translational profiling shows aberrant translational regulation in primary mesothelioma cells compared to untransformed mesothelium control cells

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