Mountain View
biomedical and healthCAre Data Discovery Index Ecosystem
help Advanced Search
Title: Expression profile of U373 cells over-expressing DTX1 and cells expressing a dominant negative form of MAML1      
dateReleased:
05-31-2012
description:
Glioblastoma multiforme (GBM) is the most malignant and most common tumor of the central nervous system characterized by rapid growth and extensive tissue infiltration. GBM results in more years of life lost than any other cancer type. Notch signaling has been implicated in GBM pathogenesis through several modes of action. Inhibition of Notch leads to a reduction of cancer-initiating cells in gliomas and reduces proliferation and migration. Deltex1 (DTX1) is part of an alternative Notch signaling pathway distinct from the canonical MAML1/RBPJκ-mediated cascade. In this study, we show that DTX1 activates both the RTK/PI3K/PKB as well as the MAPK/ERK pathway. Moreover, we found the anti-apoptotic factor Mcl-1 to be induced by DTX1. In accordance with this, the clonogenic potential and proliferation rates of glioma cell lines correlated with DTX1 levels. DTX1 knock down mitigated the tumorigenic potential in vivo, and overexpression of DTX1 increased cell migration and invasion of tumor cells accompanied by an elevation of the pro-migratory factors PKBβ and Snail1. Microarray gene expression analysis identified a DTX1-specific transcriptional program - including microRNA-21 - which is distinct from the canonical Notch signaling. We propose the alternative Notch pathway via DTX1 as oncogenic factor in malignant glioma and found low DTX1 expression levels to correlate with prolonged survival of GBM and early breast cancer patients in open source databases. We generated human glioma U373 cell lines stably expressing Enhanced Green Fluorescent Protein (EGFP), human Deltex1-Myc Tag (DTX1-myc), or Master Mind Like 1 - dominant negative (MAML1-dn) to compare differences in overall gene expression. We included 3x EGFP control samples, 3x DTX1-myc, and 3 MAML1-dn samples.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-22772
refinement:
raw
alternateIdentifiers:
22772
keywords:
functional genomics
dateModified:
08-10-2015
availability:
available
types:
gene expression
name:
Homo sapiens
ID:
A-AFFY-141
name:
Affymetrix GeneChip Human Gene 1.0 ST Array [HuGene-1_0-st-v1]
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-22772/E-GEOD-22772.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-22772/E-GEOD-22772.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22772
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress
Similar Datasets

Feedback?

If you are having problems using our tools, or if you would just like to send us some feedback, please post your questions on GitHub.