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SRP139787
Homo sapiens
48 Downloadable Samples
Illumina HiSeq 2500
Description
We decribe the accessible chormatin landscape in RAS-induced (RIS) and NOTCH induced senescence (NIS) using ATAC-seq. By expressing active NOTCH (N1ICD) in the context of RIS, we find that N1ICD antagonises the formation of accessible regions in RIS. By performing co-cultures, we demonstrate that cells expressing a NOTCH1 ligand, JAGGED1, can antagonise the formation of RIS specific accessible regions. Overall design: mRNA profiles were IMR90 cells expressing ER:HRAS(G12V) and a control vector or MSCV miR30 shHMGA1 were generated. 6 biological replicates.
Publication Title
NOTCH-mediated non-cell autonomous regulation of chromatin structure during senescence.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 23 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Methods for identifying protein-protein interactions have mostly been limited to tagged exogenous expression approaches. We now establish a rapid, robust and comprehensive method for finding interacting proteins using endogenous proteins from limited cell numbers. We apply this approach called Rapid IP-Mass Spectrometry of Endogenous proteins (RIME) to identify ER, FoxA1 and E2F4 interacting proteins in breast cancer cells. From small numbers of starting cells, we find a comprehensive collection of known ER, FoxA1 and E2F4 targets, plus a number of novel unexpected interactors. One of the most ER (and FoxA1) associated interactors is GREB1, an estrogen induced gene with almost no known function. We apply RIME, in parallel with ER ChIP-seq, to identify ER protein interactors and ER binding events from solid tumor xenografts, resulting in the validation of the ER-GREB1 interactions. Furthermore, we establish a method for identifying endogenous interacting proteins from solid primary breast cancer samples, whih we apply to validate ER interactions with GREB1 and additional co-factors. Mechanistically, we show that GREB1 is recruited with ER to the chromatin where it functions as an essential estrogen-mediated regulatory factor required for effective ER transcriptional activity. Our novel approach enables, for the first time, the ability for discovery and validation of protein-protein interactions in whole tissue and solid tumors, revealing significant insight into ER regulatory factors.
Publication Title
Endogenous purification reveals GREB1 as a key estrogen receptor regulatory factor.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 192 Downloadable Samples
- IlluminaHiSeq2000
Description
Exploring effect of progesterone/progestin treatment on gene expression Overall design: Two cell lines, three conditions (Full Media with E2, E2+ Progesterone, Full Media + R5020 Progestin)
Publication Title
Progesterone receptor modulates ERα action in breast cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 48 Downloadable Samples
- IlluminaHiSeq2000
Description
Analysis of C4-2 prostate cancer cell line after 6 hrs of treatment with TOPK-32. PBK is overexpressed in a number of solid tumours, including prostate cancer. Results provide insight into the molecular mechanisms of PBK in prostate carcinogenesis. Overall design: This experiment was designed to understand the regulation of transcriptome by PDZ domain binding kinase, which is an important kinase with role in cell cycle. The cells were treated with a catalytic inhibitor TOPK32 which inhibits the kinase activity of PBK protein.
Publication Title
A reciprocal feedback between the PDZ binding kinase and androgen receptor drives prostate cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- IlluminaHiSeq2000
Description
Analysis of C4-2 Prostate cancer cell line after 72 hours of knockdown. PBK is overexpressed in a number of solid tumours, including prostate cancer. Results provide insight into the molecular mechanisms of PBK in prostate carcinogenesis. Overall design: This experiment was designed to understand the regulation of transcriptiome by PDZ domain binding kinase (PBK), which is an important kinase with role in cell cycle. In order to achieve this, the endogenous protein was knocked down using siRNA pool that targets the PBK mRNA.
Publication Title
A reciprocal feedback between the PDZ binding kinase and androgen receptor drives prostate cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 28 Downloadable Samples
- NextSeq500, IlluminaHiSeq2000
Description
Triple negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease for which there is no targeted therapy. Here we report the preferential and high sensitivity of TNBCs to BET bromodomain inhibitors such as JQ1 manifested by cell cycle arrest in early G1, apoptosis, and induction of markers of luminal epithelial differentiation in vitro and in vivo. The sensitivity of TNBC and other tumor types to BET inhibition establishes a rationale for clinical investigation, and a motivation to understand mechanisms of resistance. After engendering acquired resistance to BET inhibition in previously sensitive TNBCs, we utilized integrative approaches to identify a unique mechanism of epigenomic resistance to this epigenetic therapy. Resistant cells remain dependent on BRD4, confirmed by RNA interference. However, TNBC cells adapt to BET bromodomain inhibition by re-recruitment of unmutated BRD4 to super-enhancers, now in a bromodomain-independent manner. Proteomic studies of resistant TNBC identify hyper-phosphorylation of BRD4 and strong association with MED1. Together, these studies provide a rationale for BET inhibition in TNBC and argue for combination strategies to anticipate clinical drug resistance. Overall design: RNA-Seq in parental and JQ1 resistant triple negative breast cancer (TNBC) in response to DMSO or JQ1 treatment over time
Publication Title
Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 48 Downloadable Samples
- IlluminaHiSeq2000
Description
Analysis of C4-2 Prostate cancer cell line after 72 hours of knockdown. CHKA is overexpressed in a number of solid tumours, including prostate cancer. Results provide insight into the molecular mechanisms of CHKA in prostate carcinogenesis. Overall design: This experiment was designed to understand the regulation of transcriptome by Choline kinase alpha (CHKA) which is an important enzyme in Kennedy pathway. In order to achieve this, the endogenous protein was knocked down using siRNA pool that targets the CHKA mRNA.
Publication Title
Choline Kinase Alpha as an Androgen Receptor Chaperone and Prostate Cancer Therapeutic Target.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 41 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Presbycusis age-related hearing loss is the number one communicative disorder of our aged population. Here we analyzed gene expression for a set of GABA receptors in the cochlea of aging CBA mice using the Affymetrix GeneChip MOE430A. Functional phenotypic hearing measures distortion-product otoacoustic emission (DPOAE) amplitudes (four age groups) were made. The gene expression changes from RMA normalized microarray data (40 replicates) were first subjected to one-way ANOVA, and then linear regression was performed. In addition, the log signal ratio was converted to fold change, and selected gene expression changes were confirmed by relative real-time PCR. Major findings: expression of GABA-A receptor subunit 6was upregulated with age and hearing loss, whereas subunit 1 was repressed. In addition, GABA-A receptor associated protein like-1 and GABA-A receptor associated protein like-2 were strongly downregulated with age and hearing impairment. Lastly, gene expression measures were correlated with pathway/network relationships relevant to the inner ear using Pathway Architect, to identify key pathways consistent with the gene expression changes observed.
Publication Title
Novel approach to select genes from RMA normalized microarray data using functional hearing tests in aging mice.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This study analyzes gene expression in beta-thalassemic fetal liver erythroblasts in the Th3 murine model. FACS-purified wild-type, heterozygous, and homozygous stage-matched erythroblasts from E14.5 fetal livers are compared.
Publication Title
Integrated protein quality-control pathways regulate free α-globin in murine β-thalassemia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 32 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Mouse inbred strains differ in many aspects of their phenotypes, and it is known that gene expression does so too. This gives us an opportunity to isolate the genetic aspect of variation in expression and compare it to other phenotypic variables. We have investigated these issues using an eight-strain expression profile comparison with four replicates per strain on Affymetrix MGU74av2 GeneChips focusing on one well-defined brain tissue (the hippocampus). We identified substantial strain-specific variation in hippocampal gene expression, with more than two hundred genes showing strain differences by a very conservative criterion. Many such genetically driven differences in gene expression are likely to result in functional differences including differences in behaviour. A large panel of inbred strains could be used to identify genes functionally involved in particular phenotypes, similar to genetic correlation. The genetic correlation between expression profiles and function is potentially very powerful, especially given the current large-scale generation of phenotypic data on multiple strains (the Mouse Phenome Project). As an example, the strongest genetic correlation between more than 200 probe sets showing significant differences among our eight inbred strains and a ranking of these strains by aggression phenotype was found for Comt, a gene known to be involved in aggression.
Publication Title
Hippocampal gene expression profiling across eight mouse inbred strains: towards understanding the molecular basis for behaviour.
Sample Metadata Fields
No sample metadata fields
View Samples