E-GEOD-66048
Ontology highlight
ABSTRACT:
PROVIDER: E-GEOD-66048 | ExpressionAtlas | 2025-01-24
REPOSITORIES: ExpressionAtlas
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| E-GEOD-66048-analysis-methods.tsv | Tabular | |||
| E-GEOD-66048-atlasExperimentSummary.Rdata | Rdata | |||
| E-GEOD-66048-configuration.xml | Xml | |||
| E-GEOD-66048-percentile-ranks.tsv | Tabular | |||
| E-GEOD-66048.condensed-sdrf.tsv | Tabular |
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Project description:G protein alpha q and 11 are mutated in 80% of uveal melanoma. We observed that treatment with the BRD4 inhibitor JQ1 resulted in different phenotypic responses in G-protein mutant uveal melanoma cell lines and wild type uveal melanoma cell lines. We used microarrarys to profile the gene expression changes occuring in wild type and mutant cell lines in response to treament with JQ1 Uveal melanoma cells were profiled in triplicate on Affymetrix Human Genome U133A 2.0 Array arrays per manufacturer's instructions
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Project description:Type II testicular germ cell cancers (GCC) are the most frequently diagnosed tumors in young men (20 - 40 years) and are classified as seminoma or non-seminoma. GCCs are commonly treated by orchiectomy and chemo- or radiotherapy. However, a subset of metastatic non-seminomas display only incomplete remission or relapse and require novel treatment options. Recent studies have shown effective application of the small-molecule inhibitor JQ1 in tumor therapy, which interferes with the function of bromodomain and extra-terminal (BET)-proteins. Here, we demonstrate that upon JQ1 doses ≥ 250 nM GCC cell lines and Sertoli cells display compromised survival and induction of cell cycle arrest. JQ1 treated GCC cell lines display upregulation of genes indicative for DNA damage and a cellular stress response. Additionally, downregulation of pluripotency factors and induction of mesodermal differentiation was detected. GCCs xenografted in vivo showed a reduction in tumor size, proliferation and angiogenesis when subjected to JQ1 treatment. The combination of JQ1 and the histone deacetylase inhibitor romidepsin further enhanced the apoptotic effect in vitro and in vivo. Thus, we propose that JQ1 alone, or in combination with romidepsin may serve as a novel therapeutic option for GCCs.
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| phs001072 | dbGaP