Filters
Technology
Platform
SRP061651
Homo sapiens
6 Downloadable Samples
Illumina HiSeq 2000
Description
Hypermethylation of tumor suppressor gene (TSG) promoters confers growth advantages to cancer cells, but how these changes arise is poorly understood. Here, we report that tumor hypoxia reduces the activity of oxygen-dependent TET enzymes, which catalyze DNA de-methylation through 5-methylcytosine oxidation. This occurs independently of hypoxia-associated alterations in TET gene expression, basal metabolism, HIF activity or nuclear reactive oxygen species, but directly depends on oxygen shortage. Hypoxia-induced loss of TET activity increases hypermethylation at gene promoters in vitro, while also in patients, gene promoters are markedly more methylated in hypoxic than normoxic tumors. Affected genes are frequently involved in DNA repair, cell cycle regulation, angiogenesis and metastasis, indicating cellular selection of hypermethylation events. Overall, up to 50% of the tumor-associated hypermethylation is ascribable to hypoxia across various cancer types. Accordingly, spontaneous murine breast tumors become hypermethylated when rendered hypoxic through vessel pruning, whereas vessel normalisation rescues this effect. Tumor hypoxia thus acts as a novel regulator underlying DNA methylation. Overall design: RNAseq of MCF7 cells grown under hypoxic and normoxic conditions. Submission includes data on 5 independent RNAseq experiments, each containing biological replicates grown under hypoxic conditions (0.5% oxygen), and under normoxic conditions.
Publication Title
Tumour hypoxia causes DNA hypermethylation by reducing TET activity.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Following androgen ablation therapy (AAT), the vast majority of prostate cancer patients develop treatment resistance with a median time of 18-24 months to disease progression. To identify molecular targets that aid in prostate cancer cell survival and contribute to the androgen independent phenotype, we evaluated changes in LNCaP cell gene expression during 12 months of androgen deprivation. At time points reflecting critical growth and phenotypic changes, we performed Affymetrix expression array analysis to examine the effects of androgen deprivation during the acute response, during the period of apparent quiescence, and during the emergence of highly proliferative, androgen-independent prostate cancer cells (LNCaP-AI). We discovered alterations in gene expression for a host of molecules associated with promoting prostate cancer cell growth and survival, regulating cell cycle progression, apoptosis and adrenal androgen metabolism, in addition to AR co-regulators and markers of neuroendocrine disease. These findings illustrate the complexity and unpredictable nature of cancer cell biology and contribute greatly to our understanding of how prostate cancer cells likely survive AAT. The value of this longitudinal approach lies in the ability to examine gene expression changes throughout the cellular response to androgen deprivation; it provides a more dynamic illustration of those genes which contribute to disease progression in addition to specific genes which constitute a malignant androgen-independent phenotype. In conclusion, it is of great importance that we employ new approaches, such as the one proposed here, to continue exploring the cellular mechanisms of therapy resistance and identify promising targets to improve cancer therapeutics.
Publication Title
Longitudinal analysis of androgen deprivation of prostate cancer cells identifies pathways to androgen independence.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
STAT5A and STAT5B proteins belong to the family of signal transducers and activators of transcription. They are encoded by 2 separate genes with 91% identity in their amino acid sequences. Despite their high degree of conservation, STAT5A and STAT5B exert non-redundant functions, resulting at least in part from differences in target gene activation. To better characterize the differential contribution of STAT5A and STAT5B in gene regulation, we performed single or double knock-down of STAT5A and STAT5B using small interfering RNA. Subsequent gene expression profiling and RT-qPCR analyses of IL-3-stimulated Ba/F3-beta cells led to the identification of putative novel STAT5 target genes. Chromatin immunoprecipitation assays analyzing the corresponding gene loci identified unusual STAT5 binding sites compared to conventional STAT5 responsive elements. Some of the STAT5 targets identified are upregulated in several human cancers, suggesting that they might represent potential oncogenes in STAT5-associated malignancies.
Publication Title
In vivo identification of novel STAT5 target genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
We have generated mouse models of real CMT1B mutations in the gene encoding for myelin protein zero (P0). One of these mutants, P0S63del is retained in the ER where it elicits an unfolded protein response (UPR). Genetic ablation of the UPR factor CHOP restores the motor capacity in S63del mice. We used microarray to decipher the molecular mechanism undelying the P0S63del neuropathy and the rescue in S63del/Chop null nerves.
Publication Title
Resetting translational homeostasis restores myelination in Charcot-Marie-Tooth disease type 1B mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Arabidopsis thaliana
- 35 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
AtGenExpress: A multinational coordinated effort to uncover the transcriptome of the multicellular model organism Arabidopsis thaliana
Publication Title
The AtGenExpress global stress expression data set: protocols, evaluation and model data analysis of UV-B light, drought and cold stress responses.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 31 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
AtGenExpress: A multinational coordinated effort to uncover the transcriptome of the multicellular model organism Arabidopsis thaliana.
Publication Title
The AtGenExpress global stress expression data set: protocols, evaluation and model data analysis of UV-B light, drought and cold stress responses.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 25 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
AtGenExpress: A multinational coordinated effort to uncover the transcriptome of the multicellular model organism Arabidopsis thaliana.
Publication Title
The AtGenExpress global stress expression data set: protocols, evaluation and model data analysis of UV-B light, drought and cold stress responses.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 26 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
AtGenExpress: A multinational coordinated effort to uncover the transcriptome of the multicellular model organism Arabidopsis thaliana.
Publication Title
The AtGenExpress global stress expression data set: protocols, evaluation and model data analysis of UV-B light, drought and cold stress responses.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 28 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
AtGenExpress: A multinational coordinated effort to uncover the transcriptome of the multicellular model organism Arabidopsis thaliana.
Publication Title
The AtGenExpress global stress expression data set: protocols, evaluation and model data analysis of UV-B light, drought and cold stress responses.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 23 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
AtGenExpress: A multinational coordinated effort to uncover the transcriptome of the multicellular model organism Arabidopsis thaliana
Publication Title
The AtGenExpress global stress expression data set: protocols, evaluation and model data analysis of UV-B light, drought and cold stress responses.
Sample Metadata Fields
Specimen part
View Samples