There is growing evidence from epidemiological and experimental studies suggesting that early life exposure to environmental chemicals can have long-term consequences that are seen in adults and not apparent early in life. We recently demonstrated that developmental exposure of zebrafish embryos to low, non-embryotoxic levels of PCB126 did not affect larval behavior but caused changes in adult behavior (Glazer et al., 2016, NeuroToxicology 52:134-143). Zebrafish embryos were exposed to either vehicle (DMSO) or low concentrations of PCB126 (0.3, 0.6, 1.2 nM) for 20 h (4–24 h post fertilization), and then reared to adulthood in clean water. Locomotor activity of the larvae at 7 and 14 days post fertilization (dpf) was not affected by PCB126. In contrast, adult fish (4 months old) tested in novel tank and shoaling assays showed impaired habituation to a novel environment. In order to investigate the underlying molecular basis of these phenotypes, we determined the transcriptional profiles in whole embryos (48 hpf), larvae (5 dpf) and adult brain (4 mo) using strand-specific RNA-sequencing. Our results show that 0.3 nM PCB126 exposure induced cyp1a transcript levels 12.5-fold in 48-hpf embryos but there was no induction in 5-dpf larvae, suggesting transient activation of aryl hydrocarbon receptor during early development. No significant induction of cyp1a was observed in the brains of adults exposed as embryos to PCB126. However, we observed significant changes in gene expression profiles in the adult brain samples. A total of 2209 and 1628 genes were differentially expressed in 0.3 nM and 1.2 nM PCB126-exposed groups, respectively. KEGG pathway analysis of differentially expressed genes in the brain suggest enrichment of genes involved in oxidative phosphorylation, neurodegenerative diseases, circadian rhythm and calcium signaling pathways. We are currently investigating the role of these genes in altered behavior observed in the adults. Overall, our results suggest that PCB exposure during sensitive periods of early development alters normal development of the brain by reprogramming gene expression patterns. [Funded by NIH P01ES021923 and NSF OCE-1314642]. Overall design: A total of 24 samples were sequenced. It includes 3 different time points and 2 or 3 different treatments. Each treatment had 3 biological replicates.
Early Life Exposure to Low Levels of AHR Agonist PCB126 (3,3',4,4',5-Pentachlorobiphenyl) Reprograms Gene Expression in Adult Brain.
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View SamplesTo determine if RU-486 would be effective as a chemopreventive agent, microarrays were used to analyse global gene expression changes in wild-type vs. MMTV-PAX8PPARg mice to determine their differential response to RU486
The chemopreventive effect of mifepristone on mammary tumorigenesis is associated with an anti-invasive and anti-inflammatory gene signature.
Specimen part, Treatment
View SamplesThe role of Sca-1 on mammary tumorigenesis was assessed. Microarrays were used to analyse global gene expression changes in Sca-1 KO mice versus wild-type mice and determine the differential responses to MP and DMBA-induced Mammary carcinogenesis
Stem cell antigen-1 deficiency enhances the chemopreventive effect of peroxisome proliferator-activated receptorγ activation.
Specimen part, Treatment
View SamplesExpression data from this experiment is part of a larger project aimed at defining the individual effects and synergistic effects of ROCK inhibitor Y-27632 and conditioned media from irradiated J2 cells when applied to epithelial cells. This data set consists of four individual samples, each of which are total RNA collected from human foreskin keratinocyte cells, either grown in F medium (control), treated with Y-27632, grown in conditioned medium (as described in associated publication), or both treatments.
Multifactorial analysis of conditional reprogramming of human keratinocytes.
Specimen part, Treatment
View SamplesThe role of PDK1 on mammary tumorigenesis and its interaction with PPARdelta, was assessed. Transgenic mice were generated in which PDK1 was expressed in the mammary epithelium.
PPARδ activation acts cooperatively with 3-phosphoinositide-dependent protein kinase-1 to enhance mammary tumorigenesis.
Specimen part, Treatment
View SamplesThe role of murine peroxisome proliferator-activated receptor-delta (PPARd) in mammary tumorigenesis was assessed. Microarrays were used to analyse global gene expression to determine changes in MMTV-PPARd transgenic mice versus wild-type mice and the effect of GW501516.
PPARδ induces estrogen receptor-positive mammary neoplasia through an inflammatory and metabolic phenotype linked to mTOR activation.
Specimen part, Treatment
View SamplesAnalysis of 2 cultured normal lung cell lines, Normal Human Bronchial Epithelial (NHBE) and Human Small Airway Epithelial (SAEC) cells (Lonza, Walkersville, MD), following treatment with 5-aza-dC to induce DNA demethylation. These results provide insight into the role of epigenetic alterations, specifically demethylation, in differential gene expression in various lung neoplasms.
Integrative discovery of epigenetically derepressed cancer testis antigens in NSCLC.
Specimen part, Cell line
View SamplesPlac1 is an X-linked (Xq26) trophoblast gene expressed at high levels in the placenta, at low levels in the testis, but not in other normal somatic tissues. However, it is re-expressed in several malignancies, including breast, colon, lung, gastric, liver and endometrial cancers as well as in most human cancer cell lines. Plac1 contains HLA-A2-restricted epitopes capable of eliciting a cytotoxic T lymphocyte (CTL) response against human breast cancer cells, and colorectal cancer patients with a Plac1-specific CTL response demonstrate long-term survival. To explore the role of Plac1 in cancer, mouse mammary tumor E0771 cells expressing high levels of Plac1 were transduced with a lentivirus expressing a Plac1 shRNA (E0771/shPlac1).
Plac1 Is a Key Regulator of the Inflammatory Response and Immune Tolerance In Mammary Tumorigenesis.
Cell line
View SamplesSoybean is a rich source of protein and oil and a primary feedstock for biodiesel production. Previous research on soybean indicated that protein, oil and yield are controlled quantitatively in soybean seeds. However, genetic mechanisms controlling seed composition and yield in soybean remain unknown. We used Affymetrix Soybean GeneChips to identify genes that are differentially expressed between developing seeds of the Minsoy and Archer soybean varieties, which differ in seed weight, yield, protein content and oil content. Some of the differentially expressed genes identified in this study may play important roles in controlling these traits.
Identification of differentially expressed genes between developing seeds of different soybean cultivars.
Specimen part
View SamplesOverexpression of miR-155 in hematological tissue leads to the onset of lymphoma, and Tet-off shutdown of this overexpression reverses the disease phenotype in mir-155LSLtTA mice. This study compares the gene expression profiles of tumors with miR-155 overexpression and withdrawal. Overall design: Examination of mRNA from 2 conditions: miR-155 overexpressing tumors and miR-155 overexpressing tumors from mice exposed to doxycycline (DOX) for 16hrs prior to harvest; samples in triplicate; tumors generated in flanks of nude mice by subcutaneous injection of splenic cells from diseased mir-155LSLtTA mice.
MicroRNA silencing for cancer therapy targeted to the tumour microenvironment.
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