Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA282141 | ENA |
REPOSITORIES: ENA
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Project description:HER2 is a tyrosine kinase receptor causally involved in cancer. A subgroup of breast cancer patients with particularly poor clinical outcome expresses a heterogeneous collection of HER2 carboxy-terminal fragments (CTFs). However, since the CTFs lack the extracellular domain that drives dimerization and subsequent activation of full-length HER2, they are in principle expected to be inactive. Here we present evidence that at low expression levels one of these fragments, 611-CTF, activated multiple signaling pathways because of its unanticipated ability to constitutively homodimerize. A transcriptomic analysis revealed that 611-CTF specifically controlled the expression of genes that we found correlated with poor prognosis in breast cancer. Among the 611-CTF-regulated genes were several that previously have been linked to metastasis, including MET, EPHA2, MMP1, IL11, ANGPTL4 and different Integrins. Transgenic mice overexpressing HER2 in the mammary gland develop tumors only after acquisition of activating mutations in the transgene. In contrast, we show that expression of 611-CTF led to development of aggressive and invasive mammary tumors without the need for mutations. These results demonstrate that 611-CTF is a potent oncogene capable of promoting mammary tumor progression and metastasis. Affymetrix Gene Array expression study, using MCF7/tet-off clones stably transfected with vectors encoding HER2 and different truncated forms of the receptor, were used to elucidate the activity of the various protein isoforms. MCF7 clones were selected, maintain and expanded in the presence of doxycycline to avoid expression of the HER2 receptor isoforms. The experiments were started by seeding equal numbers of cells in two dishes, one with and one without doxycycline. 15 or 60 hours later total RNA was isolated in parallel from the two dishes. In the dishes without doxycycline the cloned HER2 isoforms were expressed from a CMV promoter. In total 50 arrays were included in the analysis. For key clones and time points biological replicates were included.
2015-04-25 | E-GEOD-68256 | biostudies-arrayexpress
Project description:HER2 is a tyrosine kinase receptor causally involved in cancer. A subgroup of breast cancer patients with particularly poor clinical outcome expresses a heterogeneous collection of HER2 carboxy-terminal fragments (CTFs). However, since the CTFs lack the extracellular domain that drives dimerization and subsequent activation of full-length HER2, they are in principle expected to be inactive. Here we present evidence that at low expression levels one of these fragments, 611-CTF, activated multiple signaling pathways because of its unanticipated ability to constitutively homodimerize. A transcriptomic analysis revealed that 611-CTF specifically controlled the expression of genes that we found correlated with poor prognosis in breast cancer. Among the 611-CTF-regulated genes were several that previously have been linked to metastasis, including MET, EPHA2, MMP1, IL11, ANGPTL4 and different Integrins. Transgenic mice overexpressing HER2 in the mammary gland develop tumors only after acquisition of activating mutations in the transgene. In contrast, we show that expression of 611-CTF led to development of aggressive and invasive mammary tumors without the need for mutations. These results demonstrate that 611-CTF is a potent oncogene capable of promoting mammary tumor progression and metastasis. Affymetrix Gene Array expression study, using MCF7/tet-off clones stably transfected with vectors encoding HER2 and different truncated forms of the receptor, were used to elucidate the activity of the various protein isoforms.
2015-04-25 | GSE68256 | GEO
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.
| S-EPMC2531291 | biostudies-literature
Project description:Gene methylation profiling of immortalized human mesenchymal stem cells comparing HPV E6/E7-transfected MSCs cells with human telomerase reverse transcriptase (hTERT)- and HPV E6/E7-transfected MSCs. hTERT may increase gene methylation in MSCs. Goal was to determine the effects of different transfected genes on global gene methylation in MSCs.
2011-08-25 | GSE23936 | GEO
Project description:The aim of the experiment was to gain insight into the role of estrogen receptor beta (ERβ) isoforms in the response of breast cancer MCF7 cells to antiestrogens and retinoids. To this end, clones of MCF7 cells constitutively expressing human ERβ1 (MCF7-ERβ1) or ERβ2 (MCF7-ERβ2) were established and used for the determination of the global transcriptional changes induced upon treatment with hydroxytamoxifen (OHT) and all-trans retinoic acid (ATRA). Gene signatures associated with each clone will shed light to the mechanism underlying the ERβ1- and ERβ2-mediated response of MCF7 cells to antiestrogens and retinoids.
2022-12-13 | E-MTAB-12549 | biostudies-arrayexpress
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO
Project description:To study pathways associated with ferroptosis sensitivity
2022-06-01 | GSE173905 | GEO
Project description:To identify differentially regulated genes between wild-type and Pak1 deficient human breast cancer cells, we performed a comparative gene profiling study by using human whole genome arrays. We compared the gene expression profiles of MCF10A.B2 cells (MCF10A cells expressing a chemically activatable form of Her2) stably expressing a Tet inducible shRNA directed against Pak1 gene. All the experiments were performed in duplicate using tumor derived cells from two different tumors per group.
2016-07-23 | E-GEOD-71283 | biostudies-arrayexpress
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.
| S-EPMC4686780 | biostudies-literature