Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression analysis of transgenic embryos carrying the mitf-BRAFV600E allele in the presence or absence of p53 function

ABSTRACT: Investigation of expression differences between melanomas harvested from MiniCoopR-GFP versus MiniCoopR-SETDB1 transgenic zebrafish The embryos described in this study are further analyzed in a manuscript submitted for publication by White, et al. A 12 chip study comparing gene expression levels in 80hpf animals either WT (Tu), mitf-BRAFV600E, p53-/-, or mitf-BRAFV600E;p53-/- (double)

ORGANISM(S): Danio rerio

SUBMITTER: Richard White

PROVIDER: E-GEOD-24529 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

DHODH modulates transcriptional elongation in the neural crest and melanoma.

White Richard Mark RM Cech Jennifer J Ratanasirintrawoot Sutheera S Lin Charles Y CY Rahl Peter B PB Burke Christopher J CJ Langdon Erin E Tomlinson Matthew L ML Mosher Jack J Kaufman Charles C Chen Frank F Long Hannah K HK Kramer Martin M Datta Sumon S Neuberg Donna D Granter Scott S Young Richard A RA Morrison Sean S Wheeler Grant N GN Zon Leonard I LI

Nature 20110301 7339

Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural cres ...[more]

PMID: 21430780

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Project description:In this study, we subjected the phenomenon of fractional killing in a clonal population of TRAIL-sensitive cells to careful analysis. We asked whether cells that survive initial exposure to TRAIL are sensitive or resistant to subsequent treatment with TRAIL or other apoptosis-inducing agents. We observed that TRAIL survivor cells were highly resistant to a subsequent treatment with TRAIL 24hr later but that this resistance disappeared following several days in culture. Resistance did not involve downregulation of TRAIL receptors and extended to death ligands that bind different classes of receptors: TRAIL survivors were transiently resistant to FasL and vice versa. Gene expression analysis revealed that NF-kB-mediated inflammatory genes were activated in transiently resistant survivor cells leading to an inflammatory phenotype, but resistance was mediated by an independent mechanism related to changes in signaling at the DISC. Periodic exposure to TRAIL sustained resistance, demonstrating a component of induced survival signaling leading to transient acquired resistance to TRAIL. Based on these results we propose that TRAIL treatment leads to a transient adaptation in survivor cells that can be sustained in cells exposed to long-term TRAIL treatments, leading to acquired resistance. Minimizing the impact of cell-to-cell variability on TRAIL-mediated killing will thus require appropriate spacing of stimuli as well as the use of additional agents that inhibit pro-survival pathways. RNA was collected from Control (untreated) MCF10A cells, Survivors of TRAIL treatment (Day 1), Reset cells (survivors on Day 7), and Repeat cells (Survivors treated with TRAIL on 2 subsequent days). RNA was also collected from Control and Survivor MCF10A cells expressing an IKB-super-repressor construct (Addgene, Plasmid 15291; Boehm et al., 2007), or treated with caspase inhibitors. Three biological experiments were performed (on different days) with 1-2 replicates of each sample collected for each experiment. The total number of samples was 31, on 4 IlluminaRef8 BeadChips (one sample was from an unrelated experiment and was not included). The number of total replicates for each treatment is as follows: Control (7); Survivors (6); Reset (3); Repeat (3); Control-IKB-super-repressor (2); Survivors-IKB-super-repressor (2); Control-zVADinhibitor (2); Survivors-zVADinhibitor (2); Control-IETDinhibitor (2); Survivors-IETDinhibitor (2).

Dataset Information

Expression analysis of transgenic embryos carrying the mitf-BRAFV600E allele in the presence or absence of p53 function

Publications

DHODH modulates transcriptional elongation in the neural crest and melanoma.

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