Filters
Technology
Platform
GSE109021
Homo sapiens
96 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
High-throughput transcriptomic (HTTr) technologies are increasingly being used to screen environmental chemicals in vitro to identify molecular targets and provide mechanistic context for regulatory testing. The androgen receptor (AR, NR3C4) regulates male sexual development, is involved in the pathogenesis of a number of cancers, and is often the target of endocrine disruptors. Here, we describe the development and validation of a novel gene expression biomarker to identify AR-modulating chemicals using a pattern matching method. AR biomarker genes were identified by their consistent expression after exposure to 4 AR agonists and opposite expression after exposure to 4 AR antagonists. A genetic filter was used to include only those genes that were regulated by AR. Most of the resulting 51 biomarker genes were shown to be directly regulated by AR as determined by ChIP-Seq analysis of AR-DNA interactions. The biomarker was evaluated as a predictive tool using the fold-change rank-based Running Fisher algorithm which compares the expression of AR biomarker genes under various treatment conditions. Using 163 comparisons from cells treated with 98 chemicals, the biomarker gave balanced accuracies for prediction of AR activation or AR suppression of 97% or 98%, respectively. The biomarker was able to correctly classify 16 out of 17 AR reference antagonists including those that are weak and very weak. Predictions based on comparisons from AR-positive LAPC-4 cells treated with 28 chemicals in antagonist mode were compared to those from an AR pathway model based on 11 in vitro high-throughput screening assays that queried different steps in AR signaling. The balanced accuracy was 93% for suppression. Using our approach, we identified conditions in which AR was modulated in a large collection of microarray profiles from prostate cancer cell lines including 1) AR constitutively active mutants or knockdown of AR, 2) depletion of androgens by castration or removal from media, and 3) modulators that work through indirect mechanisms including suppression of AR expression. These results demonstrate that the AR gene expression biomarker could be a useful tool in HTTr to identify AR modulators in large collections of microarray data derived from AR-positive prostate cancer cell lines.
Publication Title
Identification of Androgen Receptor Modulators in a Prostate Cancer Cell Line Microarray Compendium.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 26 Downloadable Samples
Illumina HiSeq 2500
Description
We studied alterations in gene expression profiles of the MCF7 human breast cancer cells caused by bisphenol A, bisphenol AF and glyphosate using Illumina RNA sequencing platform. Overall design: Examination of endocrine disrupting effects of xenobiotics using the MCF7 cell line
Publication Title
Editor's Highlight: Transcriptome Profiling Reveals Bisphenol A Alternatives Activate Estrogen Receptor Alpha in Human Breast Cancer Cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Rattus norvegicus
- 34 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
In order to gain insight into the effects of aging on susceptibility to environmental toxins, we characterized the expression of xenobiotic metabolizing enzymes (XMEs) from the livers of male Brown Norway and F344 rats across the adult lifespan. To examine metabolic processes across lifespan after challenge with a xenobiotic compound, Brown Norway rats were exposed to 1.0 g/kg body weight toluene by oral gavage in corn oil (4ml/kg body weight) or corn oil alone.
Publication Title
Coordinated changes in xenobiotic metabolizing enzyme gene expression in aging male rats.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 17 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Diurnal temperature cycling is an intrinsic characteristic of many exposed microbial ecosystems. However, its influence on yeast physiology and transcriptome has not been studied in detail. In this study, 24-h sinoidal temperature cycles, oscillating between 12 and 30C, were imposed on anaerobic, glucose-limited chemostat cultures of Saccharomyces cerevisiae. After three diurnal temperature cycles (DTC), concentrations of glucose, and extracellular metabolites, as well as CO2-production rates showed regular, reproducible circadian rhytms. DTC also led to waves of transcriptional activation and repression, which involved one sixth of the yeast genome. A substantial fraction of these DTC-responsive genes appeared to primarily respond to changes in glucose concentration. Elimination of known glucose-responsive genes revealed overrepresentation of previously identified temperature-responsive genes as well as genes involved in cell cycle and de novo purine biosynthesis. Analyses of budding index and flow cytomery demonstrated that DTC led to a partial synchronization of the cell cycle of the yeast populations in the chemostat cultures, which was lost upon release from DTC. Comparison of DTC results with data from steady-state cultures showed that DTC was sufficiently slow to allow S. cerevisiae chemostat cultures to almost completely acclimatize their transcriptome and physiology at the DTC temperature maximum, and to approach acclimation at the DTC temperature minimum.
Publication Title
Physiological and transcriptional responses of anaerobic chemostat cultures of Saccharomyces cerevisiae subjected to diurnal temperature cycles.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Characterization of Peroxisome Proliferator-Activated Receptor alpha (PPAR(alpha)) - Independent Effects of PPAR(alpha) Activators in the Rodent Liver: Di-(2-ethylhexyl) phthalate Activates the Constitutive Activated Receptor
Publication Title
Characterization of peroxisome proliferator-activated receptor alpha--independent effects of PPARalpha activators in the rodent liver: di-(2-ethylhexyl) phthalate also activates the constitutive-activated receptor.
Sample Metadata Fields
Sex, Age, Treatment
View Samples- Mus musculus
- 120 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Analysis of livers of male and female B6C3F1 mice exposed to prototype treatments from five classes of model hepatotoxicants. These hepatotoxicants include compounds that activate the peroxisome proliferator-activated receptor (PPAR), induce the inflammatory response, activate the constitutive androstane receptor (CAR), stimulate the hypoxia signal transduction pathway, and activate the aryl-hydrocarbon receptor (AHR). The results provide insights into the shared and unique pathways that are activated across these model hepatotoxicants.
Publication Title
Screening a mouse liver gene expression compendium identifies modulators of the aryl hydrocarbon receptor (AhR).
Sample Metadata Fields
Sex, Age, Compound, Time
View Samples- Mus musculus
- 47 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
PPAR-null and wild-type male mice treated with PFHxS or PFNA
Publication Title
Screening a mouse liver gene expression compendium identifies modulators of the aryl hydrocarbon receptor (AhR).
Sample Metadata Fields
Sex, Specimen part, Compound
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Glyphosate-based herbicides are the major pesticides used worldwide. There is an intense debate on the estrogenic effects of their ingredients. We have compared the estrogenic effects of glyphosate (the active principle), polyethoxylated tallowamine (a co-formulant), and a commercial formulations containing different co-formulants to those of estradiol and bisphenol A in the MCF-7 human breast cancer cell line. The gene expression profiles were determined using the Affymetrix Human Transcriptome 2.0 Array.
Publication Title
Evaluation of estrogen receptor alpha activation by glyphosate-based herbicide constituents.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
The nuclear receptor peroxisome proliferator-activated receptor alpha (PPAR) regulates responses to chemical or physical stress in part by altering expression of genes involved in proteome maintenance. Many of these genes are also transcriptionally regulated by heat shock (HS) through activation by HS factor-1 (HSF1). We hypothesized that there are interactions on a genetic level between PPAR and the HS response mediated by HSF1. Wild-type and PPAR-null mice were exposed to HS, the PPAR agonist WY-14,643 (WY), or both; gene and protein expression was examined in the livers of the mice 4 or 24 hrs after HS. Gene expression profiling identified a number of Hsp family members that were altered similarly in both mouse strains. However, most of the targets of HS did not overlap between strains. A subset of genes was shown by microarray and RT-PCR to be regulated by HS in a PPAR-dependent manner. HS also down-regulated a large set of mitochondrial genes specifically in PPAR-null mice that are known targets of PPARg co-activator 1 (PGC-1) family members. Pretreatment of PPAR-null mice with WY increased expression of PGC-1b and target genes and prevented the down-regulation of the mitochondrial genes by HS. A comparison of HS genes regulated in our dataset with those identified in wild-type and HSF1-null mouse embryonic fibroblasts indicated that although many HS genes are regulated independently of both PPAR and HSF1, a number require both factors for HS responsiveness. These findings demonstrate that the PPAR genotype has a dramatic effect on the transcriptional targets of HS and support an expanded role for PPAR in the regulation of proteome maintenance genes after exposure to diverse forms of environmental stress including HS.
Publication Title
Analysis of the heat shock response in mouse liver reveals transcriptional dependence on the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha).
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We characterized gene expression changes in the developing mouse liver at gestational days (GD) 11.5, 12.5, 13.5, 14.5, 16.5, and 19.5 and in the neonate (postnatal day (PND) 7 and 30) using full-genome microarrays and compared these changes to that in the adult liver. The fetal liver, and to a lesser extent the neonatal liver, exhibited dramatic differences in gene expression compared to adults. Canonical pathway analysis of the fetal liver signature demonstrated increases in functions important in cell replication and DNA fidelity whereas most metabolic pathways of intermediary metabolism were suppressed. Comparison of the dataset to a number of previously published datasets revealed 1) a striking similarity between the fetal liver and that of the pancreas in both mice and humans, 2) a nucleated erythrocyte signature in the fetus and 3) suppression of most xenobiotic metabolism genes throughout development, except a number of transporters associated with expression in hematopoietic cells.
Publication Title
Transcriptional ontogeny of the developing liver.
Sample Metadata Fields
Specimen part
View Samples