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Mus musculus
6 Downloadable Samples
Illumina HiSeq 2000
Description
PI3K (phosphoinositide 3-kinase)/AKT and RAS/MAPK (mitogen-activated protein kinase) pathway coactivation in the prostate epithelium promotes both epithelial–mesenchymal transition (EMT) and metastatic castration-resistant prostate cancer (mCRPC), which is currently incurable. To study the dynamic regulation of the EMT process, we developed novel genetically defined cellular and in vivo model systems from which epithelial, EMT and mesenchymal-like tumor cells with Pten deletion and Kras activation can be isolated. When cultured individually, each population has the capacity to regenerate all three tumor cell populations, indicative of epithelial–mesenchymal plasticity. Despite harboring the same genetic alterations, mesenchymal-like tumor cells are resistant to PI3K and MAPK pathway inhibitors, suggesting that epigenetic mechanisms may regulate the EMT process, as well as dictate the heterogeneous responses of cancer cells to therapy. Among differentially expressed epigenetic regulators, the chromatin remodeling protein HMGA2 is significantly upregulated in EMT and mesenchymal-like tumors cells, as well as in human mCRPC. Knockdown of HMGA2, or suppressing HMGA2 expression with the histone deacetylase inhibitor LBH589, inhibits epithelial–mesenchymal plasticity and stemness activities in vitro and markedly reduces tumor growth and metastasis in vivo through successful targeting of EMT and mesenchymal-like tumor cells. Importantly, LBH589 treatment in combination with castration prevents mCRPC development and significantly prolongs survival following castration by enhancing p53 and androgen receptor acetylation and in turn sensitizing castration-resistant mesenchymal-like tumor cells to androgen deprivation therapy. Taken together, these findings demonstrate that cellular plasticity is regulated epigenetically, and that mesenchymal-like tumor cell populations in mCRPC that are resistant to conventional and targeted therapies can be effectively treated with the epigenetic inhibitor LBH589. Overall design: RNA was extracted from pooled Epithelial, EMT and Mesenchymal-like tumor cells isolated by FACS sorting CD45-CD31-Ter119-EpCAM+GFP-, CD45-CD31-Ter119-EpCAM+GFP+, and CD45-CD31-Ter119-EpCAM-GFP+ cells, respectively, from the prostates of 10-12 week old Pb-Cre+/-;PtenL/L;KrasG12D/+;Vim-GFP (CPKV) mice (n=17) and separated into two technical replicates. Paired-end sequencing data with read lengths of 100 bp were generated using the Illumina HiSeq2000 system.
Publication Title
HDAC inhibition impedes epithelial-mesenchymal plasticity and suppresses metastatic, castration-resistant prostate cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 43 Downloadable Samples
- Illumina HiSeq 2000
Description
Tumors driven by activation of the transcription factor Myc generally show oncogene addiction. However, the gene-expression programs that depend upon sustained Myc activity in those tumors remain unknown. We have addressed this issue in a model of liver carcinoma driven by a reversible tet-Myc transgene, combining gene expression profiling with the mapping of Myc and RNA Polymerase II on chromatin. Switching off the oncogene in advanced carcinomas revealed that Myc is required for the continuous activation and repression of distinct sets of genes, constituting no more than half of those deregulated during tumor progression, and an even smaller subset of all Myc-bound genes. We further showed that a Myc mutant unable to associate with the co-repressor protein Miz1 is defective in the initiation of liver tumorigenesis. Altogether, our data provide the first detailed analysis of a Myc-dependent transcriptional program in a fully developed carcinoma, revealing that the critical effectors of Myc in tumor maintenance must be included within defined subsets (ca. 1,300 each) of activated and repressed genes. Overall design: RNAseq samples of control liver (n=11), tet-Myc tumors (n=16), tet-Myc tumors with short-term Myc inactivation (n=8), tet-MycVD tumors (n=11)
Publication Title
Identification of MYC-Dependent Transcriptional Programs in Oncogene-Addicted Liver Tumors.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Role of beta-arrestin2 in response to intermittent or continuous parathyroid hormone (PTH) treatment.
Publication Title
Beta-arrestin2 regulates parathyroid hormone effects on a p38 MAPK and NFkappaB gene expression network in osteoblasts.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Compound
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
RNA-Seq and expression microarray highlight different aspects of the fetal amniotic fluid transcriptome.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The second trimester fetal transcriptome can be assessed based on cell-free RNA found within the amniotic fluid supernatant. The objective of this study was to compare the suitability of two technologies for profiling the human fetal transcriptome: RNA-Seq and expression microarray. Comparisons were based on total numbers of gene detected, rank-order gene expression, and functional genomic analysis.
Publication Title
RNA-Seq and expression microarray highlight different aspects of the fetal amniotic fluid transcriptome.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The objective of this study was to identify the tissue expression patterns and biological pathways enriched in term amniotic fluid cell-free fetal RNA by comparing functional genomic analyses of term and second-trimester amniotic fluid supernatants.
Publication Title
Global gene expression analysis of term amniotic fluid cell-free fetal RNA.
Sample Metadata Fields
Sex
View Samples
GSE60403- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The objective of this study was to identify the tissue expression patterns and biological pathways enriched in term cord blood fetal RNA of obese women compared to lean
Publication Title
Assessing the fetal effects of maternal obesity via transcriptomic analysis of cord blood: a prospective case-control study.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Amniotic fluid (AF) is a complex biological material that provides a unique window into the developing human. Residual AF supernatant contains cell-free fetal RNA. The objective of this study was to develop an understanding of the AF core transcriptome by identifying the transcripts ubiquitously present in the AF supernatant of euploid midtrimester fetuses.
Publication Title
The amniotic fluid transcriptome: a source of novel information about human fetal development.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
During pregnancy, cells from each fetus travel into the maternal circulation and organs, resulting in the development of microchimerism. Identification of the cell types in this microchimeric population would permit better understanding of possible mechanisms by which they affect maternal health. However, comprehensive analysis of fetal cells has been hampered by their rarity. In this study, we sought to overcome this obstacle by combining flow cytometry with multidimensional gene expression microarray analysis of fetal cells isolated from the murine maternal lung during late pregnancy. Fetal cells were collected from the lungs of pregnant female mice. cDNA was amplified and hybridized to gene expression microarrays. The resulting fetal cell core transcriptome was interrogated using multiple methods including Ingenuity Pathway Analysis, the BioGPS gene expression database, principal component analysis, the Eurexpress gene expression atlas and primary literature. Here we report that small numbers of fetal cells can be flow sorted from the maternal lung, facilitating discovery-driven gene expression analysis. We additionally show that gene expression data can provide functional information about the fetal cells. Our results suggest that fetal cells in the murine maternal lung are a mixed population, consisting of trophoblasts, mesenchymal stem cells and cells of the immune system. The detection of trophoblasts and immune cells in the maternal lung may facilitate future mechanistic studies related to the development of immune tolerance and pregnancy-related complications, such as preeclampsia. Furthermore, the presence and persistence of mesenchymal stem cells in maternal organs may have implications for long-term postpartum maternal health.
Publication Title
Comprehensive analysis of genes expressed by rare microchimeric fetal cells in the maternal mouse lung.
Sample Metadata Fields
No sample metadata fields
View Samples- 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
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