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SRP045727
Mus musculus
12 Downloadable Samples
Illumina HiSeq 2000
Description
Our findings demonstrate beneficial effects of enhancing transactivation function of the ligand-activated polyQ AR and indicate that the SUMOylation pathway may provide new targets for therapeutic intervention. Overall design: We mutated conserved lysines in the polyQ AR that are targeted by SUMO, a modification that inhibits AR transactivation function.
Publication Title
Rescue of Metabolic Alterations in AR113Q Skeletal Muscle by Peripheral Androgen Receptor Gene Silencing.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HiSeq 2000
Description
Our studies indicate that glucose and acetate can regulate histone acetylation by altering the acetyl-CoA concentrations in the cell. The purpose of this study was to to determine whether specific gene sets correlated with acetyl-CoA availability. We conclude that 10% of glucose-regulated genes are acetyl-CoA regulated genes (genes suppressed or induced by low glucose and reversed by acetate). Acetate usually regulated gene expression in the same direction as glucose, suggesting that acetyl-CoA is a key mediator of glucose-dependent gene expression. Overall design: The experiments were performed in quadruplicates for each condition with a total of 12 samples
Publication Title
Akt-dependent metabolic reprogramming regulates tumor cell histone acetylation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 89 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Antimalarials have anticancer potential. Results: We have systematically tested five distinct antimalaria drugs in a panel of cancer cell lines. Conclusion: Three antimalarial classes display potent antiproliferative activity, and their potency is correlated with cancer cell gene expression patterns. Significance: We confirm and extend anticancer potential of these antimalarials and we discuss their therapeutic potential based on clinical data.
Publication Title
Anticancer properties of distinct antimalarial drug classes.
Sample Metadata Fields
Sex, Age, Cell line
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
The goal of this study is to understand the alterations in transcriptome induced by histone H3K36M mutations Overall design: Transcritome profiling of 3 cell lines cultured in vitro and 6 murine tumors
Publication Title
Histone H3K36 mutations promote sarcomagenesis through altered histone methylation landscape.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 4000
Description
IDH1-R132H is expressed in Low Grade Glioma (LGG) in combination with loss of function mutation in ATRX and TP53 genes. IDH1-R132H results in gain of function with production of 2-hydroxygluatrate, that in turn generates a hypermethylatyed phenotype in DNA and histone with consequences in epigenetic regulation of gene expression. Here we will compare the gene expression profile between IDH1-R132H and IDH1 Wt LLG animal brain tumors in reponse to radiation Overall design: Evaluate differential gene expression between Brain DH1-R132H and IDH1 wt in response to 10Gy ionizing radiation at 14 days after tumor neurospheres implantation
Publication Title
IDH1-R132H acts as a tumor suppressor in glioma via epigenetic up-regulation of the DNA damage response.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Inactivating mutations in SMARCA4 (BRG1), a key SWI/SNF chromatin remodelling gene, underlie small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). To reveal its druggable vulnerabilities, we perform kinase-focused RNAi screens and uncover that SMARCA4-deficient SCCOHT cells are highly sensitive to the inhibition of cyclin-dependent kinase 4/6 (CDK4/6). SMARCA4 loss causes profound downregulation of cyclin D1, which limits CDK4/6 kinase activity in SCCOHT cells and leads to in vitro and in vivo susceptibility to CDK4/6 inhibitors. SCCOHT patient tumors are deficient in cyclin D1 yet retain the retinoblastoma-proficient/p16INK4a-deficient profile associated with positive responses to CDK4/6 inhibitors. Thus, our findings indicate that CDK4/6 inhibitors, approved for a breast cancer subtype addicted to CDK4/6 activation, could be repurposed to treat SCCOHT. Moreover, our study suggests a novel paradigm whereby critically low oncogene levels, caused by loss of a driver tumor suppressor, may also be exploited therapeutically. Overall design: The effect of CDK6 knockdown and palbociclib treatment on SCCOHT cells.
Publication Title
CDK4/6 inhibitors target SMARCA4-determined cyclin D1 deficiency in hypercalcemic small cell carcinoma of the ovary.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
D122p53 mice (a model of D133p53 isoform) are tumour prone, have extensive inflammation and elevated serum IL-6. To investigate the role of IL-6 we crossed 122p53 mice with IL-6 deficient mice. Here we show that loss of IL-6 reduced JAK-STAT signalling, tumour incidence, and metastasis. We also show that D122p53 activates RhoA-ROCK signalling leading to tumour cell invasion which is IL-6 dependent and can be reduced by inhibition of JAK-STAT and RhoA-ROCK pathways. Similarly, we show that 133p53 activates the these pathways, resulting in invasive and migratory phenotypes, in colorectal cancer cells. Gene expression analysis of colorectal tumours showed enrichment of GPCR signalling associated with D133TP53 mRNA. Patients with elevated D133TP53 mRNA levels had a shorter disease free survival. Our results suggest that D133p53 promotes tumour invasion by activation of the JAK-STAT and RhoA-ROCK pathways and that patients whose tumours have high D133p53 may benefit from therapies targeting these pathways.
Publication Title
∆133p53 isoform promotes tumour invasion and metastasis via interleukin-6 activation of JAK-STAT and RhoA-ROCK signalling.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 502 Downloadable Samples
- Illumina HiSeq 2500
Description
This dataset contains collected RNASeq data of 552 samples from the GOYA clinical trial. Overall design: The GOYA trial tested the efficacy of Gazyva (GA101) compared with Rituxan (Rituximab) in first line, untreated DLBCL patients. Patients were randomized 1:1 to either G or R combined with a CHOP chemotherapy backbone. Tumor samples were collected at baseline, RNA was isolated using RNA-Access, and RNASeq was run with TruSeq (Illumina) RNASeq.
Publication Title
PD-L1 and tumor-associated macrophages in de novo DLBCL.
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Natural killer (NK) cells can be divided into phenotypic subsets based on the expression of receptors that bind self-MHC-I molecules with differing affinities; a concept termed licensing or education. Here we show that NK cell subsets exhibit markedly different migratory, effector, and immunoregulatory functions on dendritic cells and antigen-specific CD8+ T cell responses during influenza and murine cytomegalovirus infections. Shortly after infection, unlicensed NK cells preferentially trafficked to draining lymph nodes and produced GM-CSF, which promoted the expansion and activation of dendritic cells, and ultimately resulted in sustained antigen-specific CD8+ T cell responses. In contrast, licensed NK cells preferentially migrated to infected parenchymal tissues and produced greater levels of interferon- (IFN-). Importantly, human NK cell subsets exhibited similar phenotypic characteristics and patterns of cytokine production. Collectively, our studies demonstrate a critical demarcation between the functions of licensed and unlicensed NK cell subsets, with the former functioning as the classical effector subset in inflamed tissues and the latter as modulators of adaptive immunity helping to prime immune responses in draining lymph nodes.
Publication Title
Licensing delineates helper and effector NK cell subsets during viral infection.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The v-erbA oncogene belongs to a superfamily of transcription factors called nuclear receptors, which includes the retinoic acid receptors (RARs) responsible for mediating the effects of retinoic acid (RA). Nuclear receptors bind to specific DNA sequences in the promoter region of target genes and v-erbA is known to exert a dominant negative effect on the activity of the RARs. The repressor activity of v-erbA has been linked to the development of hepatocellular carcinoma (HCC) in a mouse model. We have used microarray analysis to identify genes differentially expressed in hepatocytes in culture (AML12 cells) stably transfected with v-erbA and exposed to RA. We have found that v-erbA can affect expression of RA-responsive genes. We have also identified a number of v-erbA-responsive genes that are known to be involved in carcinogenesis and which may play a role in the development of HCC.
Publication Title
Modulation of expression of RA-regulated genes by the oncoprotein v-erbA.
Sample Metadata Fields
Specimen part, Cell line
View Samples