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E-MEXP-999
Rattus norvegicus
70 Downloadable Samples
Affymetrix Rat Expression 230A Array (rae230a)
Description
The rat uterus responds to acute estrogen treatment with a series of well characterized physiological responses; however, the gene expression changes required to elicit these responses have not been fully characterized. In order to understand early events induced by estrogen exposure in vivo, we evaluated the temporal gene expression in the uterus of the immature rat after a single dose of 17 Alpha-ethynyl estradiol (EE) by microarray analysis, evaluating the expression of 15,923 genes. Immature 20 day old rats were exposed to a single dose of EE (10 ug/kg) and the effect on uterine histology, weight and gene expression were determined after 1, 2, 8, 24, 48, 72 and 96 h. EE induced changes in the expression of 3,867 genes, at least at one time point (p¡Ü0.0001), and at least 1.5 fold (up- or down-regulated). Specifically, the expression of 8, 116, 3030, 2076, 381, 445, and 125 genes was modified at 1, 2, 8, 24, 48, 72 or 96 hours after exposure to EE respectively (p¡Ü0.0001, t Test). At the tissue and organ level, a clear uterotrophic response was elicited by EE after only 8 h, reaching a maximum after 24 h and remaining detectable even after 96 h of exposure. The uterine phenotypic changes were induced by sequential changes in the transcriptional status of a large number of genes, in a program that involves multiple molecular pathways. Using the gene ontology to better understand the temporal response to estrogen exposure, we determined that the earliest changes were in the expression of genes whose products are involved in transcriptional regulation and signal transduction, followed by genes implicated in protein synthesis, energy utilization, solute transport, cell proliferation and differentiation, tissue remodeling and immunological responses among other pathways. The compendium of genes here presented represents a comprehensive compilation of estrogen-responsive genes involved in the uterotrophic response.
Publication Title
Uterine temporal response to acute exposure to 17alpha-ethinyl estradiol in the immature rat.
Sample Metadata Fields
Sex, Age, Specimen part, Compound, Time
View Samples- Danio rerio
- 39 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Genomic, proteomic, and metabolomic technologies continue to receive increasing interest from environmental toxicologists. This interest is due to the great potential of these technologies to identify detailed modes of action and to provide assistance in the evaluation of a contaminant’s risk to aquatic organisms. Our experimental model is the zebrafish (Danio rerio) exposed to reference endocrine disrupting compounds in order to investigate compound-induced changes in gene transcript profiles. Adult, female zebrafish were exposed to 0, 15, 40, and 100 ng/L of 17 alpha-ethynylestradiol (EE2) and concentration and time-dependent changes in hepatic gene expression were examined using Affymetrix GeneChip® Zebrafish Genome Microarrays. At 24, 48, and 168 hours, fish were sacrificed and liver mRNA was extracted for gene expression analysis (24 and 168 hours only). In an effort to link gene expression changes to effects on higher levels of biological organization, body and ovary weights were measured and blood was collected for measurement of plasma steroid hormones (17 beta-estradiol (E2), testosterone (T)) and vitellogenin (VTG) using ELISA. EE2 exposure significantly affected GSI, E2, T, VTG and gene expression. We observed 1575 genes that were significantly affected (up- or down-regulated by at least 1.5-fold (p ? 0.001) in a concentration-dependent manner by EE2 exposure at either 24 or 168 hours. EE2 exposure altered transcription of genes involved in steroid hormone homeostasis, cholesterol homeostasis, retinoic acid metabolism, and cell growth and proliferation. Plasma VTG was significantly increased at 24, 48, and 168 hours (p<0.05) at 40 and 100 ng/L and at 15 ng/L at 168 hours. E2 and T were significantly reduced following EE2 exposure at 48 and 168 hours. GSI was decreased in a dose-dependent manner at 168 hours. In this study, we identified genes involved in a variety of biological functions that have the potential to be used as markers of exposure to estrogenic substances. Future work will evaluate the use of these genes in zebrafish exposed to weak estrogens to determine if these genes are indicative of exposure to estrogens with varying potencies.
Publication Title
Hepatic gene expression profiling using Genechips in zebrafish exposed to 17alpha-ethynylestradiol.
Sample Metadata Fields
Sex, Specimen part, Compound, Time
View Samples- Rattus norvegicus
- 118 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a), Affymetrix Rat Genome U34 Array (rgu34a)
Description
The purpose of this study was to determine 1) the transcriptional program elicited by exposure to three estrogen receptor (ER) agonists: 17 a-ethynyl estradiol (EE), genistein (Ges) and bisphenol A (BPA) during fetal development of the rat testis and epididymis; and 2) whether very low dosages of estrogens (evaluated over five orders of magnitude of dosage) produce unexpected changes in gene expression (i.e., a non-monotonic dose-response curve). In three independently conducted experiments, Sprague-Dawley rats were dosed (s.c.) with 0.001-10mg EE/kg/day, 0.001-100 mg Ges/kg/day or 0.002-400mg BPA/kg/day. While morphological changes in the developing reproductive system were not observed, the gene expression profile of target tissues were modified in a dose-responsive manner. Independent dose-response analyses of the three studies identified 56 genes that are significantly modified by EE, 28 genes by Ges and 15 genes by BPA (out of 8740). Even more genes were observed to be significantly changed when only the high dose is compared with all lower doses: 141, 46 and 67 genes, respectively. Global analyses aimed at detecting genes consistently modified by all of the chemicals identified 52 genes whose expression changed in the same direction across the three chemicals. The dose-response curve for gene expression changes was monotonic for each chemical, with both the number of genes significantly changed and the magnitude of change, for each gene, decreasing with decreasing dose. Using the available annotation of the gene expression changes induced by ER-agonist, our data suggest that a variety of cellular pathways are affected by estrogen exposure. These results indicate that gene expression data are diagnostic of mode of action and, if they are evaluated in the context of traditional toxicological end-points, can be used to elucidate dose-response characteristics.
Publication Title
Gene expression changes induced in the testis by transplacental exposure to high and low doses of 17{alpha}-ethynyl estradiol, genistein, or bisphenol A.
Sample Metadata Fields
Sex, Age, Specimen part, Compound
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Combination of platinum-based chemotherapy and radiation is currently the standard treatment for locally advanced lung cancer patients. However, therapeutic resistance to these therapies may arise from the presence of cancer stem cells (CSCs). To investigate the CSCs hypothesis of chemo-radiation resistance, we used microarray assay to profile CSCs-like cisplatin-resistant lung cancer cells (CDDP-R) versus its parental cells. CDDP-R cells were established by exposing H460 lung cancer cells to 3M cisplatin for 7 days, followed by 0.8% methylcellulose selection over 14 consecutive days.We found that CDDP-R cells expressed higher levels of stem cell markers, including CD133 and ALDH. They are more resistant to cisplatin- and etoposide-induced apoptosis and to high radiation dose (20Gy). Clonogenic assays suggest that CDDP-R cells were more resistant to radiation than parental H460 cells (DER=1.21, p<0.01). Xenograft studies suggest that CDDP-R cells were more tumorigenic (p<0.001). Microarray and comprehensive protein interaction networks analyses revealed IGFBP3 as a highly ranked hub protein which plays an important role in the mechanism of cisplatin resistance. We found reduced level of IGFBP3 and enhanced IGFR-1 activation upon IGF stimulation in CDDP-R cells. The specific targeting of IGF-1R using siRNA resulted in significant sensitization of CDDP-cells (DER=1.17, p<0.05) to radiation compared with the parental H460 cells. Our findings suggest that CDDP-R cells have the characteristics of CSCs and constitute a suitable model to study lung CSCs. Profiling of CSCs-like H460 cells led to the identification of IGF as an important pathway for chemo- and radiotherapy resistance in lung cancer.
Publication Title
Role of insulin-like growth factor-1 signaling pathway in cisplatin-resistant lung cancer cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Multispecies miRNA-3 Array (mirna3), Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Molecular pathogenesis of post-transplant acute kidney injury: assessment of whole-genome mRNA and miRNA profiles.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 424 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Background: Obesity is a risk factor for breast cancer in postmenopausal women and is associated with decreased survival and less favorable clinical characteristics such as greater tumor burden, higher grade, and poor prognosis, regardless of menopausal status. Despite the negative impact of obesity on clinical outcome, molecular mechanisms through which excess adiposity influences breast cancer etiology are not well-defined.
Publication Title
Effect of obesity on molecular characteristics of invasive breast tumors: gene expression analysis in a large cohort of female patients.
Sample Metadata Fields
Disease stage
View Samples- Rattus norvegicus
- 20 Downloadable Samples
Illumina HiSeq 2500
Description
Gene expression analysis of hypothalami from female animals at different juvenile developmental reproductive stages. Results provide insight into the role of the hypothalamus in controlling the onset of puberty. Overall design: SD rats were housed (8/cage) in a controlled environment and euthanized at different ages (PND=7, PND=14, Early Juvenile: 21 days, Late Juvenile: 28 days, Late Proestus (the day of first ovulation): 30-33 days. Rats were anesthetized and brains were rapidly removed. The medial basal hypothalamus (MBH) was dissected away from the rest of the brain and flash frozen. Total RNA was isolated from each sample using Qiagen''s RNeasy Mini Kit (Valencia, CA). Samples were bioanalyzed on a RNA 6000 Nano chip kit to check for integrity and concentration before sending it to OHSU''s Massively Parallel Sequencing Shared Resource for library preparation and sequencing.
Publication Title
Trithorax dependent changes in chromatin landscape at enhancer and promoter regions drive female puberty.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The hematopoietic microenvironment consists of non-hematopoietic derived stromal elements and hematopoietic derived monocytes and macrophages which interact and function together to control the proliferation and differentiation of early blood-forming cells. Two human stromal cell lines (HS-5 and HS-27a) representing distinct functional components of this microenvironment have been extensively characterized and shown to influence monocyte gene expression. This series of gene expression profiles is intended to extend the previous studies and identify which gene expression changes may require cell-cell contact or occur in the stromal cells as a result of monocyte influence;or in the monocytes as a result of stormal influences.
Publication Title
Functionally and phenotypically distinct subpopulations of marrow stromal cells are fibroblast in origin and induce different fates in peripheral blood monocytes.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The bone marrow microenvironment is a complex mixture of cells that function in concert to regulate hematopoiesis. Cellular components include fixed nonhematopoietic stromal elements as well as monocytes and resident macrophages, which are derived from the hematopoietic stem cells. Although these monocyte-lineage cells are reported to modify stromal cell function, the reverse also occurs. Given the secretory capability of the monocyte/macrophage and their various potential functions, it is not surprising that stromal cells contained within a particular niche can modify monocyte gene expression and functional maturation.
Publication Title
Functionally and phenotypically distinct subpopulations of marrow stromal cells are fibroblast in origin and induce different fates in peripheral blood monocytes.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 6 Downloadable Samples
Description
Androgen receptor (AR) is typically overexpressed in castration-resistant prostate cancer (CRPC). CRPC-derived VCaP cells display an excessive number of chromatin AR-binding sites (ARBs). This study analyzed direct transcription programs of the AR, the prevalence of AR enhancers and the transcriptional regulators involved in the regulation of at the enhancer regions. The analysis utilized global nuclear run-on sequencing (GRO-seq). The GRO-seq data were integrated with the ARB and VCaP cell-specific transcription factor-binding data. Androgen in 30 min activated and repressed transcription of a large number of genes including novel AR targets IGF-1 receptor and EGF receptor. GRO-seq analysis also revealed that only a fraction of the ARBs resides at functional enhancers. Activation of AR bound enhancers was most potent at the sites that also bound PIAS1, ERG and HDAC3. Our genome-wide data provide new insights how AR can directly control growth-signaling pathways in CPRC cells. Overall design: ChIP-seq samples were collected from cells treated with vehicle (ethanol, EtOH) or 10 nM R1881 (synthetic androgen methyltrienolone). IgG sample was collected from EtOH- and R1881-treated cells and used as background control. Biological duplicate samples of the AR (R1881-treated) and CTCF (vehicle- and R1881-treated) ChIP-seq samples were analyzed by using Illumina HiSeq 2000 platform 1.9. Single IgG and H3K9me3 (R1881-treated) samples were analyzed with the same platform. GRO-seq was used to determine androgen-induced changes in nascent transcription in VCaP and LNCaP cells.
Publication Title
Global analysis of transcription in castration-resistant prostate cancer cells uncovers active enhancers and direct androgen receptor targets.
Sample Metadata Fields
No sample metadata fields
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