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GSE70770
Homo sapiens
199 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip, Affymetrix Genome-Wide Human SNP 6.0 Array (genomewidesnp6)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integration of copy number and transcriptomics provides risk stratification in prostate cancer: A discovery and validation cohort study.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Homo sapiens
- 199 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Background
Publication Title
Integration of copy number and transcriptomics provides risk stratification in prostate cancer: A discovery and validation cohort study.
Sample Metadata Fields
Disease
View Samples- Homo sapiens
- 25 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
5-hydroxymethylcytosine marks promoters in colon that resist DNA hypermethylation in cancer.
Sample Metadata Fields
Sex, Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The ETS family member GABPα modulates androgen receptor signalling and mediates an aggressive phenotype in prostate cancer.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
In prostate cancer, the androgen receptor (AR) is a key transcription factor at all disease stages. We recently showed that during progression to castrate-resistant prostate cancer the AR acquires the ability to bind to a distinct set of genomic sites in tissue samples and that some of the genes that are regulated by the AR in these conditions correlate with poor prognosis. Based on this work we hypothesised that the AR is reprogrammed through interactions with other transcription factors. In the present study we show that GABP, an ETS transcription factor which is upregulated in CRPC, is an AR-interacting transcription factor. Ectopic expression of GABPA in prostate cancer cell-lines enables them to acquire some of the molecular and cellular characteristics of CRPC tissues as well as more aggressive growth phenotypes.
Publication Title
The ETS family member GABPα modulates androgen receptor signalling and mediates an aggressive phenotype in prostate cancer.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 30 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
The androgen receptor (AR) is the dominant growth factor in prostate cancer. Understanding how it regulates the human transcriptome is of paramount importance. The early effects of castration on human prostate cancer have not previously been studied. In this study 27 patients were medically castrated with degarelix seven days before radical prostatectomy. Resected tumour was compared with matched controlled untreated prostate cancer tissue by means of mass spectrometry, immunohistochemistry and gene expression array (validated by RT-PCR). All patients had castrate levels of serum androgen with reduced levels of intra-prostatic androgen at prostatectomy. Differential expression of known androgen regulated genes (TMPRSS2, KLK3, CAMKK2, FKBP5) was observed. We identified 749 genes downregulated and 908 genes upregulated following castration. AR regulation of AMACR expression and three other genes (FAM129A, RAB27A and KIAA0101) was confirmed. Up-regulation of oestrogen receptor alpha (ESR1) expression was observed in malignant epithelia. This was associated with differential expression of ESR1 regulated genes and correlated with proliferation (Ki67 expression).
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 25 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
The discovery of cytosine hydroxymethylation (5-hmC) as a mechanism that potentially controls DNA methylation changes typical of neoplasia prompted us to investigate its behavior in colon cancer. 5-hmC is globally reduced in proliferating cells such as colon tumors and the gut crypt progenitors, from which tumors can arise. Here, we show that colorectal tumors and cancer cells express Ten-Eleven Translocation (TET) transcripts at levels similar to normal tissues. Genome-wide analyses show that promoters marked by 5-hmC in normal tissue, and those identified as TET2 targets in colorectal cancer cells, are resistant to methylation gain in cancer. In vitro studies of TET2 in cancer cells confirm that these promoters are resistant to methylation gain independently of sustained TET2 expression. We also find that a considerable number of the methylation gain-resistant promoters marked by 5-hmC in normal colon overlap with those that are marked with poised bivalent histone modifications in embryonic stem cells. Together our results indicate that promoters that acquire 5-hmC upon normal colon differentiation are innately resistant to neoplastic hypermethylation by mechanisms that do not require high levels of 5-hmC in tumors. Our study highlights the potential of cytosine modifications as biomarkers of cancerous cell proliferation.
Publication Title
5-hydroxymethylcytosine marks promoters in colon that resist DNA hypermethylation in cancer.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Nuclear ARRB1 induces pseudohypoxia and cellular metabolism reprogramming in prostate cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina HumanWG-6 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina HumanWG-6 v3.0 expression beadchip
Description
It is becoming clear that interconnected functional gene networks, rather than single genes in isolation, govern stem cell self-renewal and differentiation. To identify potential epigenetic networks that impact on human epidermal stem cells we performed siRNA based genetic screens for 332 chromatin modifiers. We developed a Bayesian mixture model to predict putative functional interactions between those epigenetic modifiers that regulated differentiation. This allowed us to discover a network of genetic interactions involving EZH2, UHRF1 (both known to regulate epidermal self-renewal), ING5 (a MORF complex component), BPTF and SMARCA5 (NURF complex components). Genome-wide localisation and global mRNA expression analysis revealed that these factors impact two distinct but functionally related gene sets, including integrin extracellular matrix receptors that mediate anchorage of epidermal stem cells to their niche. Using a competitive epidermal reconstitution assay we confirmed that ING5, BPTF, SMARCA5, EZH2 and UHRF1 control differentiation under physiological conditions. Thus, regulation of distinct gene expression programs through the interplay between diverse epigenetic strategies protects epidermal stem cells from differentiation.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples