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GSE32892
Homo sapiens
11 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The androgen receptor plays a critical role throughout the progression of prostate cancer and is an important drug target for this disease. While chromatin immunoprecipitation coupled with massively parallel sequencing (ChIP-Seq) is becoming an essential tool in studying transcription and chromatin modification factors, it has rarely been employed in the context of drug discovery. Here we report the first publicly available genome-wide and dose-dependent inhibition landscape of AR binding by drug-like small molecules including correlation with binding strength using ChIP-Seq. Integration of sequence analysis, transcriptome profiling, cell viability assays and in vivo tumor inhibition studies enabled us to establish a direct cistrome-activity relationship for two novel potent AR antagonists. By selectively occupying the strongest binding sites, AR signaling remains active even when low androgen levels are low, a scenario characteristic of first-line androgen ablation therapy. Coupled cistrome and transcriptome profiling upon small molecule antagonism led to the identification of not only key direct downstream effectors of AR but also their mode of regulation: unbiased pathway mapping revealed that AR is a key modulator of steroid metabolism by forming a tightly controlled feedback loop with other nuclear receptor family members. Furthermore, we found AR has an extensive role in negative gene regulation and estrogen (related) receptor likely mediates its function as a transcriptional repressor. In conclusion, our study provides a global and dynamic view of ARs regulatory program upon antagonism, which may serve as a molecular basis for deciphering and developing AR therapeutics.
Publication Title
Dose-dependent effects of small-molecule antagonists on the genomic landscape of androgen receptor binding.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 46 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP) are the 2 most common forms of idiopathic interstitial pneumonia. Response to therapy and prognosis are remarkably different. The clinical-radiographic distinction between IPF and NSIP may be challenging. We sought to investigate the gene expression profile of IPF vs. NSIP
Publication Title
Comprehensive gene expression profiling identifies distinct and overlapping transcriptional profiles in non-specific interstitial pneumonia and idiopathic pulmonary fibrosis.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Saccharomyces cerevisiae
- 59 Downloadable Samples
Illumina HiSeq 2000, Illumina HiSeq 2500
Description
We show that aneuploidy is common in wild isolates of yeast, which are inherently tolerant to chromosome amplification and down-regulate expression at 40% of amplified genes. To dissect the mechanism of this dosage response, we generated isogenic strain panels in which diploid cells carried either two, three, or four copies of the affected chromosomes. Using a mixture of linear regression (MLR) model to classify genes, we find that expression is actively down regulated in proportion to increased gene copy at up to 30% of genes. Genes subject to dosage control are under higher expression constraint – but show elevated rates of gene amplification – in wild populations, suggesting that dosage compensation buffers copy number variation (CNV) at toxic genes Overall design: RNA-seq and transcriptome analysis of S. cerevisiae natural isolates having aneuploidy. Technical triplicate was performed for isogenic diploid strains having 2, 3 and 4 copies of a given chromosome (strain panels), while technical duplicate or singulate was performed on all other aneuploids.
Publication Title
Dosage compensation can buffer copy-number variation in wild yeast.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
In this dataset, we included expression data obtained from 30 resected human PDAC tumors, to examine what genes are differentially expressed in different cohorts that might lead to various outcomes
Publication Title
Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
<i>Airn</i> Regulates Igf2bp2 Translation in Cardiomyocytes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cancer cells express different sets of receptor type tyrosine kinases. These receptor kinases may be activated through autocrine or paracrine mechanisms. Fibroblasts may modify the biologic properties of surrounding cancer cells through paracrine mechansms.
Publication Title
The role of HGF/MET and FGF/FGFR in fibroblast-derived growth stimulation and lapatinib-resistance of esophageal squamous cell carcinoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To elucidate the function of Airn isoforms in the heart, we conducted RNA immunoprecipitation experiment followed by microarray (RIP-chip) in murine cardiomoycyte cell line HL-1.
Publication Title
<i>Airn</i> Regulates Igf2bp2 Translation in Cardiomyocytes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To elucidate the function of Airn isoforms in the heart, we conducted loss-of-function experiments in murine cardiomoycyte cell line HL-1.
Publication Title
<i>Airn</i> Regulates Igf2bp2 Translation in Cardiomyocytes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression from pre- and post- Cediranib treated patients with metastatic Alveolar Soft Part Sarcoma (ASPS)
Publication Title
Cediranib for metastatic alveolar soft part sarcoma.
Sample Metadata Fields
Time
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A novel long non-coding RNA Myolinc regulates myogenesis through TDP-43 and Filip1.
Sample Metadata Fields
Cell line, Time
View Samples