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SRP108222
Homo sapiens
8 Downloadable Samples
Illumina HiSeq 2500
Description
Androgen receptor (AR) signaling is a distinctive feature of prostate cancer (PC) and represents the major therapeutic target for the treatment of metastatic disease. Though highly effective, AR antagonism has the potential to generate tumors that bypass a functional requirement for AR activity. We show here that a phenotypic shift has occurred in metastatic PCs with the emer-gence of a double-negative AR-null neuroendocrine-null phenotype that is notable for MAPK and FGF pathway activity. To identify mechanisms capable of sustaining PC survival, we gener-ated a model system designated AR program-independent prostate cancer (APIPC) which re-sists AR-targeted therapeutics, lacks neuroendocrine features, expresses high levels of FGF8 and the ID1 oncogene, and activates MAPK signaling. Pharmacological blockade of MAPK or FGF signaling inhibited APIPC tumor growth, supporting FGF/MAPK as a therapeutic avenue for treating AR-null PC. Overall design: RNA sequencing of human prostate tumor cell lines using the Illumina TruSeq Library prep and sequenced on Illumina HiSeq 2500.
Publication Title
Androgen Receptor Pathway-Independent Prostate Cancer Is Sustained through FGF Signaling.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Integration of high-risk human papillomavirus (HRHPV) into the host genome is a key event in cervical neoplastic progression. Integration is associated with deregulated expression of the viral oncogenes E6 and E7 and acquisition of a selective growth advantage for cells containing integrants. Overexpression of the viral transcriptional regulator E2 from heterologous promoters has an inhibitory effect on transcription from integrated HRHPV. We therefore hypothesised that loss of E2-expressing episomes from cells in which integration had previously occurred would be required for such cells to gain a growth advantage. Using the unique W12 model of cervical squamous carcinogenesis, we show that cells containing integrated HPV16 reproducibly emerged during long-term culture when there had been a rapid fall in episome numbers. During the period of emergence it is possible to isolate single-cell clones containing an intracellular mixture of the integrant being selected and episomes at reduced load. Microarray analysis showed that episome loss was closely associated with endogenous activation of antiviral response genes that are also inducible by the type I interferon (IFN) pathway. Taken together, our results indicate that episome loss, associated with induction of antiviral response genes, is a key event in the spontaneous selection of cervical keratinocytes containing integrated HPV16. We conclude that cervical carcinogenesis requires not only HRHPV integration, but also loss of inhibitory episomes.
Publication Title
Selection of cervical keratinocytes containing integrated HPV16 associates with episome loss and an endogenous antiviral response.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 76 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We sought to apply the technologies of gene expression profiling to detect genes significant in the aetiology of cervical carcinoma . We investigated 14 normal (NAD), 11 low grade squamous intrapepithelial lesions (LSIL), 21 high grade squamous intraepithelial lesions (HSIL) and 28 squamous cell carcinomas by Affymetrix GeneChip whole transcriptome profiling. Two SCC cell lines were also included in the cohort. Normal and SILS were profiled using the Affymetrix U133A platform, while SCCs and Cell lines were profiled using the Affymetrix U133A plus 2.0 array.
Publication Title
Gain and overexpression of the oncostatin M receptor occur frequently in cervical squamous cell carcinoma and are associated with adverse clinical outcome.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
We report bulk RNAseq of in vitro cultured horizontal basal cells, and in vivo isoalted respiratory basal cells of the murine olfactory epithelium, and compared their profiles with pre-existing bulk RNAseq of in vivo isolated HBCs and single cell RNAseq of in vivo HBCs. Overall design: RNAseq of in vitro horizontal basal cells (HBCs) in triplicate under control conditions, and FACS isolated in vivo respiratory basal cells in singlet
Publication Title
Activating a Reserve Neural Stem Cell Population In Vitro Enables Engraftment and Multipotency after Transplantation.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 74 Downloadable Samples
- IlluminaHiSeq2000
Description
We used RNA sequencing to profile over 70 transcriptomes of CD4+ T cells, a cell type crucial for Coeliac Disease CD pathogenesis, in both stimulated and resting samples from individuals with CD and unaffected controls The data gave us the opportunity to (i) compare gene expression between cases and controls; (ii) specifically assess whether genes that have been genetically associated with the disease were being DE; (iii) and also look for known and novel aspects of pathogenesis in the transcriptome of this specific cellular compartment. Overall design: RNA sequencing was performed on mRNA extracted from the CD4+ T cells of 15 Coeliac patients and 11 Controls that had been stimulated with anti-CD3/anti-CD28, PMA and left unstimulated. In total we sequenced 74 transcriptome samples using 50bp reads on an Illumina HiSeqâ„¢ 2000.
Publication Title
Transcriptome Analysis of CD4+ T Cells in Coeliac Disease Reveals Imprint of BACH2 and IFNγ Regulation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Although gain of chromosome-5p is one of the most frequent DNA copy number imbalances in cervical squamous cell carcinoma (SCC), the genes that drive its selection remain poorly understood. In a previous cross-sectional clinical study we showed that the microRNA processor Drosha (located on chromosome-5p) demonstrates frequent copy-number gain and over-expression in cervical SCC, associated with altered microRNA profiles. Here, we have conducted gene depletion/over-expression experiments to demonstrate the functional significance of up-regulated Drosha in cervical SCC cells. Drosha depletion by RNA-interference (RNAi) produced significant, specific reductions in cell motility/invasiveness in vitro, with a silent RNAi-resistant Drosha mutation providing phenotype rescue. Unsupervised hierarchical clustering following global profiling of 319 microRNAs in eighteen cervical SCC cell line specimens generated two groups according to Drosha expression levels. Altering Drosha levels in individual SCC lines changed the group into which the cells clustered, with gene depletion effects being rescued by the RNAi-resistant mutation. Forty-five microRNAs showed significant differential expression between the groups, including four of fourteen that were differentially-expressed in association with Drosha levels in clinical samples. miR-31 up-regulation in Drosha over-expressing samples/cell lines was the highest-ranked change (by adjusted p-value) in both analyses, an observation validated by Northern blotting. These functional data support the role of Drosha as an oncogene in cervical SCC, by affecting expression of cancer-associated microRNAs that have the potential to regulate numerous protein-coding genes.
Publication Title
Functional evidence that Drosha overexpression in cervical squamous cell carcinoma affects cell phenotype and microRNA profiles.
Sample Metadata Fields
Sex, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Comparison of mRNA expression profiles in W12 Series 1 cervical ectokeratinocytes at passage number 22 versus 19 (during which time the cells gain an invasive phenotype)
Publication Title
Functional evidence that Drosha overexpression in cervical squamous cell carcinoma affects cell phenotype and microRNA profiles.
Sample Metadata Fields
Sex, Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Androgen receptor gene expression in prostate cancer is directly suppressed by the androgen receptor through recruitment of lysine-specific demethylase 1.
Sample Metadata Fields
Sex, Cell line, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarray experiments were performed for VCaP and VCS2 cells with and without androgen stimulation
Publication Title
Androgen receptor gene expression in prostate cancer is directly suppressed by the androgen receptor through recruitment of lysine-specific demethylase 1.
Sample Metadata Fields
Sex, Cell line, Treatment
View Samples- Homo sapiens
- 72 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
The type II Oncostatin M receptor (OSMR) serves as the main binding site for the pleiotropic cytokine OSM. We have previously demonstrated a positive correlation between copy number driven OSMR over-expression and adverse clinical outcome in cervical tumours and have also established enhanced angiogenic, migratory and invasive potential as major consequences of OSMR over-expression using cell-line models of cervical cancer. By analysis of gene expression patterns in cell lines and tumours, this study now systematically defines cohorts of genes that are implicated for the phenotypes observed. Importantly, we have identified 15 OSM induced genes that are involved in at least one of these key functions and are up-regulated in both OSMR over-expressing cell-lines and tumours. These genes can serve as markers of OSM signalling in OSMR over-expressing SCCs and represent suitable targets for functional characterisation.
Publication Title
Overexpression of the oncostatin M receptor in cervical squamous cell carcinoma cells is associated with a pro-angiogenic phenotype and increased cell motility and invasiveness.
Sample Metadata Fields
Sex, Cell line, Time
View Samples