Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA112545 | ENA |
REPOSITORIES: ENA
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Project description:Our aim was to identify time-dependent changes in gene expression associated with Epidermal Growth Factor (EGF) and Hergulin B1 (HRG) stimulation of normal human mammary luminal epithelial cells (HB4a) and a derivative cell line (C3.6)overexpressing the receptor tyrosine kinase ErbB2/HER2. Serum-starved HB4a parental cells and ErbB2-overexpressing C3.6 cells were stimulated with EGF or HRG for 4 h, 18 h and 24 h or left unstimulated (0 h) prior to microarray analysis of mRNA levels of 9,932 probes, representing ~6,000 genes. Four replicates of each sample were co-hybridized to chips with a common RNA reference allowing direct comparison of gene expression across all experimental conditions: time, growth factor and cell line.
2006-08-15 | E-TABM-106 | biostudies-arrayexpress
Project description:Sharing common ErbB/HER receptor signaling pathway, heregulin (HRG) induces differentiation of MCF-7 breast cancer cells while epidermal growth factor (EGF) elicits proliferation. Although the cell fate led by those two ligands was totally different, the gene expression profile in early transcription was unexpectedly qualitatively similar, suggesting that the gene expression in late transcription, not early transcription, may reflect a respect of ligand specificity. In this study, based on the data from time-course microarray of all human genes, we predicted and determined a series of transcription factors which may control HRG-specific timed-late transcription and cellular differentiation of MCF-7 cells. Validation analyses showed that one of activator protein 1 (AP-1) families appeared just after c-Fos expression, another AP-1 family partner, induced expression of another transcription factor through activation of AP-1 complex. Furthermore, expression of this transcription factors caused suppression of extracellular signal-regulated kinase (ERK) phosphorylation which is sustainedly regulated by HRG-initiated ErbB signaling. Overall, our analysis indicated an importance of formation of timed-transcriptional regulatory network and its function to control upstream signaling pathway through negative feedback for cellular differentiation. Experiment Overall Design: MCF7 human breast cancer cells were stimulated by the growth hormone (epidermal growth factor (EGF) or heregulin (HRG)). Control was set as non-treated cells.
2008-10-26 | E-GEOD-13009 | biostudies-arrayexpress
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
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Project description:Trastuzumab therapy in HER2+ breast cancer patients have mixed success owing to acquired resistance to therapy. In this study, we investigate the cellular mechanisms underlying acquired resistance using -sensitive and -resistant cancer cells (BT474 and BT474R) treated with endogenous ligands EGF and HRG, across time. Our measurements probe early receptor organization through microscopy, signaling events through multi-omic measurements and assess the cellular energetic state through mitochondrial measurements. Our integrative analyses of these multimodal measurements highlight differential mechanisms in both cell lines in response to ligands. In BT474, an active PI3K-AKT-mTORC1 signaling contributes to an active mitochondrial bioenergetic state (glycolysis and lipid metabolism) for both ligands EGF and HRG. A HIF1A mediated increase in cellular bioenergetics is also seen. In BT474R, there is a ligand-dependent activation of signaling cascades. In EGF treated BT474R, an EGFR driven IRF1/STAT1/STAT2 activation with likely impact on cellular bioenergetics is seen, whilst an AR mediated alteration of lipid metabolism is pronounced after HRG treatment.
2024-02-14 | GSE237605 | GEO
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO
Project description:As the evolution of miRNA genes has been found to be one of the important factors in formation of the modern type of man, we performed a comparative analysis of the evolution of miRNA genes in two archaic hominines, Homo sapiens neanderthalensis and Homo sapiens denisova, and elucidated the expression of their target mRNAs in bain.A comparative analysis of the genomes of primates, including species in the genus Homo, identified a group of miRNA genes having fixed substitutions with important implications for the evolution of Homo sapiens neanderthalensis and Homo sapiens denisova. The mRNAs targeted by miRNAs with mutations specific for Homo sapiens denisova exhibited enhanced expression during postnatal brain development in modern humans. By contrast, the expression of mRNAs targeted by miRNAs bearing variations specific for Homo sapiens neanderthalensis was shown to be enhanced in prenatal brain development.Our results highlight the importance of changes in miRNA gene sequences in the course of Homo sapiens denisova and Homo sapiens neanderthalensis evolution. The genetic alterations of miRNAs regulating the spatiotemporal expression of multiple genes in the prenatal and postnatal brain may contribute to the progressive evolution of brain function, which is consistent with the observations of fine technical and typological properties of tools and decorative items reported from archaeological Denisovan sites. The data also suggest that differential spatial-temporal regulation of gene products promoted by the subspecies-specific mutations in the miRNA genes might have occurred in the brains of Homo sapiens denisova and Homo sapiens neanderthalensis, potentially contributing to the cultural differences between these two archaic hominines.
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