P38alfa and ATF2 act differentially depending on DUSP1 expression in NCSCL in response to cisplatin
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE26704 | GEO | 2012/01/01
SECONDARY ACCESSION(S): PRJNA136161
REPOSITORIES: GEO
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Project description:DUSP1 is involved in different cellular pathways including cancer cell proliferation, angiogenesis, invasion and resistance to chemotherapy. To gain insight into the cellular signaling pathways involving DUSP1 actions and the response to Cisplatin (CDDP) in non small cell lung cancer (NSCLC), we have used a double strategy that combines microarray and SiRNA technology. This strategy provided a differential expression profile of genes involved in CDDP response in NSCLC cell line regulated by DUSP1 using H460 and H460cri and a time course to CDDP. KEYWORDS: Expression profiling by array in cells with genetic modification in response to CCDP treatment The human non small lung cancer cell line H460 used in this study was from ATCC (American Type Culture Collection). The cell line was maintained in RPMI (Gibco, Invitrogen) supplemented with 10% bovine serum and transfected by Lipofectamine Plus Reagent from Life Technologies as directed by the manufacturer. The DUSP1 pSuperRetro-derived vectors were constructed as described (Chattoppadhyay et al., 2006). Clones expressing siRNA for DUSP1 were selected for their ability to grow in the presence of puromycin and kept for selection. Stable transfection was confirmed by Western blotting. We analyzed the differences in expression of 47000 genes in H460 cells expressing DUSP1SiRNA (H460cri) compared with the parental cell line H460pSuperRetro vector (H460v) after 0, 1, 3 and 6 hours of CDDP exposure, in order to know the different pathways that were activated by CDDP treatment dependent on expression of DUSP1. RNA was extracted and quality control was checked before hybridization on Affymetrix microarrays.
2012-01-01 | E-GEOD-26704 | biostudies-arrayexpress
Project description:DUSP1 is involved in different cellular pathways including cancer cell proliferation, angiogenesis, invasion and resistance to chemotherapy. To understand more about the cellular responses regulated by DUSP1 in NSCLC cells, we interfered DUSP1 expression in the NSCLC cell line H460 and studied the changes in gene expression differentially regulated by this phosphatase. Keywords: Expression profiling by array in cells with genetic modification
2010-12-09 | GSE19592 | GEO
Project description:DUSP1 is involved in different cellular pathways including cancer cell proliferation, angiogenesis, invasion and resistance to chemotherapy. To understand more about the cellular responses regulated by DUSP1 in NSCLC cells, we interfered DUSP1 expression in the NSCLC cell line H460 and studied the changes in gene expression differentially regulated by this phosphatase. Keywords: Expression profiling by array in cells with genetic modification The human non small lung cancer cell line H460 used in this study was from ATCC (American Type Culture Collection). The cell line was maintained in RPMI (Gibco, Invitrogen) supplemented with 10% bovine serum and transfected by Lipofectamine Plus Reagent from Life Technologies as directed by the manufacturer. The DUSP1 pSuperRetro-derived vectors were constructed as described (Chattoppadhyay et al., 2006). Clones expressing siRNA for DUSP1 were selected for their ability to grow in the presence of puromycin and kept for selection. Stable transfection was confirmed by Western blotting. RNA was extracted and quality control was checked before hybridization on Affymetrix microarrays.
2010-12-09 | E-GEOD-19592 | biostudies-arrayexpress
Project description:DUSP1 is involved in different cellular pathways including cancer cell proliferation, angiogenesis, invasion and resistance to chemotherapy. To gain insight into the cellular signaling pathways involving DUSP1 actions and the response to Cisplatin (CDDP) in non small cell lung cancer (NSCLC), we have used a double strategy that combines microarray and SiRNA technology. This strategy provided a differential expression profile of genes involved in CDDP response in NSCLC cell line regulated by DUSP1 using H460 and H460cri and a time course to CDDP. KEYWORDS: Expression profiling by array in cells with genetic modification in response to CCDP treatment The human non small lung cancer cell line H460 used in this study was from ATCC (American Type Culture Collection). The cell line was maintained in RPMI (Gibco, Invitrogen) supplemented with 10% bovine serum and transfected by Lipofectamine Plus Reagent from Life Technologies as directed by the manufacturer. The DUSP1 pSuperRetro-derived vectors were constructed as described (Chattoppadhyay et al., 2006). Clones expressing siRNA for DUSP1 were selected for their ability to grow in the presence of puromycin and kept for selection. Stable transfection was confirmed by Western blotting. We analyzed the differences in expression of 47000 genes in H460 cells expressing DUSP1SiRNA (H460cri) compared with the parental cell line H460pSuperRetro vector (H460v) after 0, 1, 3 and 6 hours of CDDP exposure, in order to know the different pathways that were activated by CDDP treatment dependent on expression of DUSP1. RNA was extracted and quality control was checked before hybridization on Affymetrix microarrays.
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Project description:Activation of the Mitogen activated protein kinase (MAPK) cascade following Toll-like receptor (TLR) stimulation enables innate immune cells to rapidly activate cytokine gene expression. A balanced response to signals of infectious danger requires that cellular activation is transient. Here, we identify the MAPK phosphatase Dual specificity phosphatase-1 (DUSP1) as an essential endogenous regulator of the inflammatory response to LPS. DUSP1-deficient (DUSP1-/-) bone marrow derived macrophages showed selectively prolonged activation of p38 MAPK and increased cytokine production. Intraperitoneal challenge of DUSP1-/- mice with LPS caused increased lethality and overshooting production of IL-6 and TNF. Transcriptional profiling revealed that DUSP1 controls a significant fraction of LPS-induced genes, that includes IL-6 and IL-10 as well as the chemokines CCL3, CCL4 and CXCL2. In contrast, the expression of the important mediators of endotoxin lethality, IFN? and IL-12, was not significantly altered by the absence of DUSP1. These data together demonstrate a specific regulatory role of DUSP1 in controlling a subset of LPS-induced genes that determines the outcome of endotoxin shock. Experiment Overall Design: Mice were injected intraperitoneally with E. coli LPS (10µg/g bodyweight) and sacrificed 6h later. Total spleen RNA (5 µg) was prepared, labeled and hybridized to Affymetrix MOE430A 2.0 GeneChips according to the manufacturer's instructions. Three biological replicates per condition were analysed. CEL Files were processed for global normalization and generation of expression values using the rma algorithm in the R affy package (www.bioconductor.org).
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Project description:Stress-activated protein kinases (SAPK) have been associated with sensorineural hearing loss (SNHL) of multiple etiologies. The activity of these kinases is tightly regulated by the dual-specificity phosphatase 1 (DUSP1), thus, DUSP1 loss of function leads to the sustained activation of SAPK. In the hearing organ, DUSP1 is an indispensable component of the stress response machinery, and its deficit accelerates SNHL progression, triggers the inflammatory response and promotes hair cell (HC) and spiral neurons (SGN) death. Here, we have studied the link between inflammation and redox imbalance in the cochlea by further characterizing the transcriptome of the Dusp1-/- mouse. RNAseq and subsequent GSEA indicated that Dusp1-/- mice present a distinct gene expression pattern of key cellular programs, including altered expression of genes of the inflammatory response and glutathione metabolism. To dissociate both components, Dusp1-/- mice were treated with the antioxidant N-acetylcysteine (NAC). Treatment with NAC delayed the onset of SNHL and reduced cochlear damage. Less HC were TUNEL+ and SGN showed less p-H2AX foci. NAC treatment not only improved redox balance but also reduced cytokine production and macrophage recruitment in Dusp1-/ -mice. In conclusion, our data point to DUSP1 as an essential node to control the cross-regulation of oxidative stress and inflammation.
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