Alzheimer's disease (AD) is characterized by massive neurodegeneration and multiple changes in cellular processes, including neurogenesis. Proteolytic processing of the amyloid precursor protein (APP) plays a central role in AD. Due to varying APP processing, several beta-amyloid peptides are generated. In contrast to the form with 40 amino acids, the variant with 42 amino acids is thought to be the pathogenic form triggering the pathophysiological cascade in AD. Here, we studied the transcriptomic response to increased or decreased Abeta42 levels generated in human neuroblastoma cells. Genome-wide expression profiles (Affymetrix)were used to analyze the cellular response to the changed Abeta42 and Abeta40-levels. <br></br><br></br>Human neuroblastoma cell line SH-SY5Y is a thrice cloned (SK-N-SH -> SH-SY -> SH-SY5 -> SH-SY5Y) subline of the neuroblastoma cell line SK-N-SH which was isolated and established in 1970. This cell line has 47 chromosomes. The cells possess a unique marker comprised of a chromosome 1 with a complex insertion of an additional copy of a 1q segment into the long arm, resulting in trisomy of 1q. The cell lines used in this study are SHSY5Y transfected with the constructs pCEP-C99I45F, pCEP-C99V50F, pCEP-C99 wildtype or mock transfected with an empty vector. Independent cell clones of each transfected line were used to provide biological replicates.<br></br> Overexpressed C99 I45F is intracellularly cleaved resulting in high Abeta42, but low Abeta40 levels.<br></br> Overexpressed C99V50F is intracellularly cleaved resulting in low Abeta42, but high Abeta40 levels.<br></br>Overexpressed C99 wildtype is intracellularly cleaved resulting in medium Abeta42 and Abeta40 levels<br></br>Mock is the SHSY5Y cell line transfected with the empty vector pCEP (Invitrogen) as a negative control
New Alzheimer amyloid beta responsive genes identified in human neuroblastoma cells by hierarchical clustering.
Cell line, Subject
View SamplesDespite their importance, plant MAP kinase targets are still poorly elucidated. Here, the specific in vivo interaction of an ethylene response factor (ERF104) with the Arabidopsis MAP kinase, MPK6, is shown by fluorescence resonance energy transfer. The interaction, which is lost within minutes after treatment with the flagellin-derived flg22 peptide, is dependent on both MPK6 kinase activity and rapid ethylene signaling initiated downstream of MPK6 activation. ERF104 is an MPK6 substrate and phosphorylation site mutations affected its stability. ERF104 activates promoters with GCC elements. This was evident from microarray data of overexpressing transgenic plants, where promoters of up regulated genes contain GCC motifs and chromatin immunoprecipitation showing ERF104 association with PDF1.2 promoter. The ERF104 overexpressor did not affect biotrophic bacteria proliferation but was more susceptible to necrotrophic Botrytis cinerea. Microarray performed with erf104 or mpk6 revealed only a limited number of flg22-induced genes that require these elements - possibly as a
Flg22 regulates the release of an ethylene response factor substrate from MAP kinase 6 in Arabidopsis thaliana via ethylene signaling.
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Glioblastoma Cell Malignancy and Drug Sensitivity Are Affected by the Cell of Origin.
Specimen part
View SamplesThe cell of origin in glioblastoma is not formally proven but generally accepted to be a neural stem cell or glial precursor cell. In addition, there is also limited knowledge about the functional consequences of the cell of origin for glioblastoma development and response to therapy.
Glioblastoma Cell Malignancy and Drug Sensitivity Are Affected by the Cell of Origin.
Specimen part
View SamplesThe cell of origin in glioblastoma is not formally proven but generally accepted to be a neural stem cell or glial precursor cell. In addition, there is also limited knowledge about the functional consequences of the cell of origin for glioblastoma development and response to therapy.
Glioblastoma Cell Malignancy and Drug Sensitivity Are Affected by the Cell of Origin.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Clonal Variation in Drug and Radiation Response among Glioma-Initiating Cells Is Linked to Proneural-Mesenchymal Transition.
Specimen part, Cell line
View SamplesIntra-tumor heterogeneity is a hallmark of glioblastoma multiforme, and thought to negatively affect treatment efficacy. Here we establish libraries of glioma-initiating cell (GIC) clones from patient samples and find extensive molecular and phenotypic variability between clones, including a wide range of responses to radiation and drugs. This widespread variability was observed as a continuum of multitherapy resistance phenotypes linked to a proneural-to-mesenchymal shift in the transcriptome.
Clonal Variation in Drug and Radiation Response among Glioma-Initiating Cells Is Linked to Proneural-Mesenchymal Transition.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The Human Glioblastoma Cell Culture Resource: Validated Cell Models Representing All Molecular Subtypes.
Disease, Cell line
View SamplesTo explore the degree to which the glioma cell lines remained transcriptionally stable under diverse experimental conditions, we transplanted three different lines (U3020MG, U3047MG and U3065MG) intracranially to NOD-SCID mice; explanted the resulting tumors and cultured the cells for two passages, and then isolated RNA from the cell line prior to transplantation (U3020MG-p10, U3047MG-p7, U3065MG-p10), from the xenograft tumor and from the explanted cells.
The Human Glioblastoma Cell Culture Resource: Validated Cell Models Representing All Molecular Subtypes.
Disease
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