Response of mouse mammary epithelial cells to treatment with MMP3
ROS-induced epithelial-mesenchymal transition in mammary epithelial cells is mediated by NF-kB-dependent activation of Snail.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Regulation of epithelial-mesenchymal transition in breast cancer cells by cell contact and adhesion.
Specimen part, Cell line
View SamplesResponse of mouse mammary epithelial cells to different cell densities and treatment with MMP3
Regulation of epithelial-mesenchymal transition in breast cancer cells by cell contact and adhesion.
Specimen part, Cell line
View SamplesResponse of mammary epithelial cells to different cell densities
Regulation of epithelial-mesenchymal transition in breast cancer cells by cell contact and adhesion.
Specimen part, Cell line
View SamplesThe NF1 tumor suppressor encodes a RAS GTPase-Activating Protein (RasGAP). Accordingly, deregulated RAS signaling underlies the pathogenesis of NF1-mutant cancers. However, while various RAS effector pathways have been shown to function in these tumors, it is currently unclear which specific proteins within these broad signaling pathways represent optimal therapeutic targets. Here we identify mTORC1 as the key PI3K pathway component in NF1-mutant nervous system malignancies and conversely show that mTORC2 and AKT are dispensable. We also report that combined mTORC1/MEK inhibition is required to promote tumor regression in animal models, but only when the inhibition of both pathways is sustained. Transcriptional profiling studies were also used to establish a predictive signature of effective mTORC1/MEK inhibition in vivo. Within this signature, we unexpectedly found that the glucose transporter gene, GLUT1, was potently suppressed but only when both pathways were effectively inhibited. Moreover, unlike VHL and LKB1 mutant cancers, reduction of 18F-FDG uptake measured by FDG-PET required the effective suppression of both mTORC1 and MEK. Together these studies identify optimal and sub-optimal therapeutic targets in NF1-mutant malignancies and define a non-invasive means of measuring combined mTORC1/MEK inhibition in vivo, which can be readily incorporated into clinical trials.
Defining key signaling nodes and therapeutic biomarkers in NF1-mutant cancers.
Specimen part
View SamplesAdam17, a shedding protease, is strongly upregtulated during inflammation and cancer. Here we investigate the genome wide effects of Adam17 knock out on the transcriptome.
Critical role of the disintegrin metalloprotease ADAM17 for intestinal inflammation and regeneration in mice.
Specimen part
View SamplesPurpose: We investigated the tetrachloroethylene associated changes in kidney transcriptomes among healthy mice, nonalcoholic fatty liver disease mice, and nonalcoholic steatohepatitis mice. Overall design: Male C57BL/6J mice were fed a low-fat diet (4% fat), high-fat diet (31% fat), or methionine/choline/folate deficient diet. Following an 8-week diet, mice were administered either a single dose of tetrachloroethylene (PERC, 300 mg/kg/d in 5% Alkamuls-EL620 in saline, 5 mL/kg) and euthanized at 24 hours post dose, or five consecutive daily doses of PERC or vehicle (n=8/diet/treatment) and euthanized at 4hours post dose. The harvested kidneys were subjected to mRNA sequencing using Illumina Hiseq 2500. Jac-NASH-063 was excluded from analysis because it did not have a good yield.
Modulation of Tetrachloroethylene-Associated Kidney Effects by Nonalcoholic Fatty Liver or Steatohepatitis in Male C57BL/6J Mice.
Cell line, Treatment, Subject
View SamplesWe report the effect of NAFLD on liver gene expression changes that could impact tetrachloroethhylene metabolism Methods: We fed male C57Bl/6J mice a base diet (BD), high fat (HFD), or methionine/choline/folate deficient high fat diet (MCD) for 8 weeks and then treated them with vehicle or tetrachloroethylene (PERC, 300 mg/kg ig). We only report "basal" differences herein (aka vehicle-treated). Results: We report that there were diet-specific differences in xenobiotic metabolizing genes, and that these genes may be responsible for NAFLD-induced disruption in PERC metabolism Overall design: Examination of liver left lobe gene expression for 3 different diets fed to C57Bl/6J male mice
Impact of Nonalcoholic Fatty Liver Disease on Toxicokinetics of Tetrachloroethylene in Mice.
Sex, Cell line, Treatment, Subject
View SamplesWe report our results of RNA-seq analysis on freshly isolated, sorted subsets of cytotoxic lymphocytes Overall design: RNA was isolated from sorted cells. Libraries were created using standard Illumina reagents and analyzed using a HiSeq2500.
ARID5B regulates metabolic programming in human adaptive NK cells.
Specimen part, Subject
View SamplesmTOR and HDAC inhibitors induce cell death of malignant peripheral nerve sheath tumors (MPNSTs) in vitro, and in vivo
mTOR and HDAC Inhibitors Converge on the TXNIP/Thioredoxin Pathway to Cause Catastrophic Oxidative Stress and Regression of RAS-Driven Tumors.
Cell line, Treatment
View Samples