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| Status |
Public on Jun 01, 2012 |
| Title |
Expression data from U373 cells expressing EGFP, MAML1-dn and DTX1-myc |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
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.
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| Contributor(s) |
Huber RM, Merlo A |
| Citation(s) |
23451269 |
| Submission date |
Jul 06, 2010 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Roland Martin Huber |
| E-mail(s) |
roland.huber@unibas.ch
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| Phone |
+41 61 265 9209
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| Organization name |
University of Basel
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| Department |
Biomedicine
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| Lab |
Molecular Neuro-Oncology
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| Street address |
Hebelstrasse 20
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| City |
Basel |
| State/province |
BS |
| ZIP/Postal code |
4031 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA128263 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE22772_RAW.tar |
33.6 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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