Cutaneous melanoma first metastasizes into sentinel lymph nodes that control the lymphatic drain from the area of the primary tumor. This observation is used clinically for melanoma patients with primary melanomas thicker than 1mm (tumor stage T2a), for these patients sentinel lymph node biopsy has become an important and routinely performed diagnostic procedure. The importance of sentinel node analysis is reflected by a significant better prognosis of melanoma patients with tumor free sentinel nodes compared to patients with metastatic sentinel nodes. Although intensively studied, not much is known about mechanisms responsible for the development of melanoma metastasis.To analyze gene expression in mouse SLNs of M24met tumor bearing animals as compared to tumor free control animals, SLNs were taken at different time points and analyzed for the presence of human M24met to classify SLNs into control, negative, macro metastatic SLN. After categorized SLNs were subjected to microarray analysis.
No associated publication
Specimen part
View SamplesRegulation of gene expression at the post-transcriptional level plays an indispensable role during TGFbeta-induced EMT and metastasis. This regulation involves a transcript-selective translational regulatory pathway in which a ribonucleoprotein (mRNP) complex, consisting of heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) and eukaryotic elongation factor 1A1 (eEF1A1), binds to a 3-UTR regulatory BAT (TGF activated translation) element and silences translation of Dab2 and ILEI mRNAs, two transcripts which are involved in mediating EMT. TGFbeta activates a kinase cascade terminating in the phosphorylation of hnRNP E1, by isoform-specific stimulation of protein kinase B/Akt2, inducing the release of the mRNP complex from the 3-UTR element, resulting in the reversal of translational silencing and increased expression of Dab2 and ILEI transcripts.
Establishment of a TGFβ-induced post-transcriptional EMT gene signature.
Specimen part
View SamplesGene expression profiling of newborn lung tissue revealed few changes in compound FGFR3/FGFR4 deficient mice, consistent with their normal lung morphology at birth, suggesting the sequence of events leading to the phenotype initiates after birth in this model.
Fibroblast growth factor receptors control epithelial-mesenchymal interactions necessary for alveolar elastogenesis.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Enhancer variants reveal a conserved transcription factor network governed by PU.1 during osteoclast differentiation.
Specimen part
View SamplesRegulator of sex-limitation (rsl) is a recessive mouse phenotype in which the otherwise male-specific sex-limited protein (Slp) gene is expressed in females. Positional cloning in rsl mice led to the identification of mutations in two neighboring KRAB zinc finger transcriptional repressors, Rsl1 and Rsl2, and BAC transgenic rescue experiements verified their ability to repress male-specific genes in the liver.
No associated publication
Sex
View SamplesHow secondary CD4 T cell effectors, derived from resting memory cells, differ from primary cells, derived from nave precursors, and how such differences impact recall responses to pathogens is unknown.
Memory CD4+ T-cell-mediated protection depends on secondary effectors that are distinct from and superior to primary effectors.
Specimen part
View SamplesNuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that induces a battery of cytoprotective genes in response to oxidative/electrophilic stress. Kelch-like ECH associating protein 1 (Keap1) sequesters Nrf2 in the cytosol. The purpose of this study was to investigate the role of Nrf2 in regulating the mRNA of genes encoding drug metabolizing enzymes and xenobiotic transporters. Microarray analysis was performed in livers of Nrf2-null, wild-type, Keap1-knockdown mice with increased Nrf2 activation, and Keap1-hepatocyte knockout mice with maximum Nrf2 activation. In general, Nrf2 did not have a marked effect on uptake transporters, but the mRNAs of organic anion transporting polypeptide 1a1, sodium taurocholate cotransporting polypeptide, and organic anion transporter 2 were decreased with Nrf2 activation. The effect of Nrf2 on cytochrome P450 (Cyp) genes was minimal, with only Cyp2a5, Cyp2c50, Cyp2c54, and Cyp2g1 increased, and Cyp2u1 decreased with enhanced Nrf2 activation. However, Nrf2 increased mRNA of many other phase-I enzymes, such as aldo-keto reductases, carbonyl reductases, and aldehyde dehydrogenase 1. Many genes involved in phase-II drug metabolism were induced by Nrf2, including glutathione S -transferases, UDP- glucuronosyltransferases, and UDP-glucuronic acid synthesis enzymes. Efflux transporters, such as multidrug resistance-associated proteins, breast cancer resistant protein, as well as ATP-binding cassette g5 and g8 were induced by Nrf2. In conclusion, Nrf2 markedly alters hepatic mRNA of a large number of drug metabolizing enzymes and xenobiotic transporters, and thus Nrf2 plays a central role in xenobiotic metabolism and detoxification.
Effect of graded Nrf2 activation on phase-I and -II drug metabolizing enzymes and transporters in mouse liver.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
No associated publication
Age
View SamplesActivation of the canonical Wnt signaling pathway is commonly observed in pancreatic cancer. We therefore sought to identify a gene expression profile associated with the activation of this pathway in pancreatic cancer cells.
Activation of WNT/β-Catenin Signaling Enhances Pancreatic Cancer Development and the Malignant Potential Via Up-regulation of Cyr61.
Specimen part, Cell line
View SamplesEpithelial Hedgehog (Hh) ligands regulate several aspects of fetal intestinal organogenesis and emerging data implicate the Hh pathway in inflammatory signaling in adult colon. We investigated the effects of chronic Hh inhibition in vivo and profiled molecular pathways acutely modulated by Hh signaling in the intestinal mesenchyme.
Hedgehog is an anti-inflammatory epithelial signal for the intestinal lamina propria.
Specimen part
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