Mature messenger RNAs (mRNAs) consist of coding sequence (CDS) and 5’ and 3’ untranslated regions, typically expected to show similar abundance within a given neuron. Examining mRNA from defined neurons we unexpectedly show extremely common unbalanced expression of cognate 3’ UTR and CDS sequences, observing many genes with high UTR relative to CDS, and others with high CDS to UTR. By in situ hybridization 19 of 19 genes examined show a broad range of UTR to CDS expression ratios in different neurons and other tissues. These ratios may be spatially graded or change with developmental age, but are consistent across animals. Further, for two genes examined, a UTR to CDS ratio above a particular threshold in any given neuron correlated with reduced or undetectable protein expression. Our findings raise questions about the role of isolated UTR sequences in regulation of protein expression, and highlight the importance of separately examining UTR and CDS sequences in gene expression analyses. Overall design: dopamine or serotonin neuronal mRNA was purified selectively by using dopamine transporter (DAT) and SLC6A4 (serotonin transporter) BacTrap mice. RNA sequencing was carried out using Illumina HiSeq 2500.
Widespread Differential Expression of Coding Region and 3' UTR Sequences in Neurons and Other Tissues.
Specimen part, Subject
View SamplesAffymetrix Hu133 GeneCHIP Microarray data for Control and c-MYC knock-down (KD) human cancer cell lines.
Novel c-MYC target genes mediate differential effects on cell proliferation and migration.
No sample metadata fields
View SamplesMuscle tissue was longitudinally characterized histologically for electron transport function by staining 1mm of quadriceps muscle at 70 micron intervals for the activities of two complexes in the mitochondrial electron transport chain, Cytochrome C Oxidase and Succinate Dehydrogenase. Unstained serial cryosections were prepared for Laser Capture Microdissection. Target cells from the serial sections were isolated and pooled for RNA extraction, amplification and hybridization on Affymetrix microarrays. We selected homogeneous populations of muscle fibers for expression profiling based upon the presence/absence of electron transport dysfunction caused by the somatic accumulation of mitochondrial DNA deletion mutations.
Mitochondrial biogenesis drives a vicious cycle of metabolic insufficiency and mitochondrial DNA deletion mutation accumulation in aged rat skeletal muscle fibers.
Age, Specimen part
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Targeting fibroblast growth factor receptors blocks PI3K/AKT signaling, induces apoptosis, and impairs mammary tumor outgrowth and metastasis.
Specimen part
View Samples4T1 mouse mammary carcinoma cells have an autocrine FGFR active loop leading to constitutive activation of downstream signaling pathways. We found that FGFR inhibitors have a strong effect on the proliferation and survival of these cells.
Targeting fibroblast growth factor receptors blocks PI3K/AKT signaling, induces apoptosis, and impairs mammary tumor outgrowth and metastasis.
Specimen part
View Samples4T1 mouse mammary carcinoma cells have an autocrine FGFR active loop leading to constitutive activation of downstream signaling pathways. We found that FGFR inhibitors have a strong effect on 4T1 tumors in-vivo.
Targeting fibroblast growth factor receptors blocks PI3K/AKT signaling, induces apoptosis, and impairs mammary tumor outgrowth and metastasis.
Specimen part
View SamplesThe tyrosine kinase receptors HER2 and HER3 play an important role in breast cancer. The HER2/HER3 heterodimer is a critical oncogenic unit associated with reduced relapse-free and decreased overall survival. We provide gene expression profile of the mammary epithelial cells MCF10A expressing HER2, HER3 or HER2/HER3 and grown in three-dimensional cultures for 15 days in the presence of heregulin, a known HER3-ligand that stabilizes and activates the HER2/HER3 heterodimer.
Co-expression of HER2 and HER3 receptor tyrosine kinases enhances invasion of breast cells via stimulation of interleukin-8 autocrine secretion.
Cell line
View SamplesExtracellular matrix interactions play essential roles in normal physiology and many pathological processes. Here, we report a novel screening platform capable of measuring phenotypic responses to combinations of ECM molecules. While the importance of ECM interactions in metastasis is well documented, systematic approaches to identify their roles in distinct stages of tumorigenesis have not been described. Using a genetic mouse model of lung adenocarcinoma, we measured the ECM-dependent adhesion of tumor-derived cells. Hierarchical clustering of adhesion profiles generated using this platform differentially segregated metastatic cell lines from primary tumor lines. Furthermore, we uncovered that metastatic cells selectively associate with fibronectin when in combination with galectin-3, galectin-8, or laminin. These interactions appear to be mediated in part by 31 integrin both in vitro and in vivo. We show that these galectins also correlate with human disease at both a transcriptional and histological level. Thus, our in vitro platform allowed us to interrogate the interactions of metastatic cells with their surrounding environment, and identified ECM and integrin interactions that could lead to therapeutic targets for metastasis prevention.
A combinatorial extracellular matrix platform identifies cell-extracellular matrix interactions that correlate with metastasis.
Specimen part
View SamplesMetastasis is the deadliest phase of cancer progression. Experimental models using immunodeficient mice have been used to gain insights into the mechanisms of metastasis. We report here the identification of a metastasis aggressiveness gene expression signature derived using human melanoma cells selected based on their metastatic potentials in a xenotransplant metastasis model. Comparison with expression data from human melanoma patients shows that this metastasis gene signature correlates with the aggressiveness of melanoma metastases in human patients. Many genes encoding secreted and membrane proteins are included in the signature, suggesting the importance of tumor-microenvironment interactions during metastasis.
Gene expression changes in an animal melanoma model correlate with aggressiveness of human melanoma metastases.
No sample metadata fields
View SamplesMetastasis is the deadliest phase of cancer progression. Experimental models using immunodeficient mice have been used to gain insights into the mechanisms of metastasis. We report here the identification of a metastasis aggressiveness gene expression signature derived using human melanoma cells selected based on their metastatic potentials in a xenotransplant metastasis model. Comparison with expression data from human melanoma patients shows that this metastasis gene signature correlates with the aggressiveness of melanoma metastases in human patients. Many genes encoding secreted and membrane proteins are included in the signature, suggesting the importance of tumor-microenvironment interactions during metastasis.
Gene expression changes in an animal melanoma model correlate with aggressiveness of human melanoma metastases.
No sample metadata fields
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