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| Status |
Public on Feb 24, 2015 |
| Title |
Genomically amplified Akt3 activates DNA repair pathway and promotes glioma progression |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Akt is a robust oncogene that plays key roles in the development and progression of many cancers, including glioma. We evaluated the differential propensities of the Akt isoforms toward progression in the well-characterized RCAs/Ntv-a mouse model of PDGFB-driven low grade glioma. A constitutively active myristoylated form of Akt1 did not induce high-grade glioma (HGG). In stark contrast, Akt2 and Akt3 showed strong progression potential with 78% and 97% of tumors diagnosed as HGG, respectively. We further revealed that significant variations in polarity and hydropathy values among the Akt isoforms in both the pleckstrin homology domain (P domain) and regulatory domain (R domain) were critical in mediating glioma progression. Gene expression profiles from representative Akt-derived tumors indicated dominant and distinct roles for Akt3, consisting primarily of DNA repair pathways. TCGA data from human GBM closely reflected the DNA repair function, as Akt3 was significantly correlated with a 76 gene signature DNA repair panel. Consistently, compared to Akt1 and Akt2 overexpression models, Akt3-expressing human GBM cells had enhanced activation of DNA repair proteins, leading to increased DNA repair and subsequent resistance to radiation and temozolomide. Given the wide range of Akt3-amplified cancers, Akt3 may represent a key resistance factor.
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| Overall design |
5 different experimental conditions were compared (including GFP, PDGFB, PDGFB in conjunciton with Akt1, Akt2, or Akt3) with 3 mice per treatment
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| Contributor(s) |
Turner KM, Hu L |
| Citation(s) |
25737557 |
| Submission date |
Feb 23, 2015 |
| Last update date |
May 10, 2018 |
| Contact name |
Kristen Turner |
| Organization name |
Ludwig Institute for Cancer Research
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| Department |
Molecular Pathology
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| Lab |
Paul Mischel
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| Street address |
9500 Gilman Dr
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| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92093 |
| Country |
USA |
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| Platforms (1) |
| GPL4134 |
Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Feature Number version) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA276065 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE66177_RAW.tar |
6.6 Mb |
(http)(custom) |
TAR |
| GSE66177_akt_1_1.txt.gz |
14.3 Mb |
(ftp)(http) |
TXT |
| GSE66177_akt_1_2.txt.gz |
14.4 Mb |
(ftp)(http) |
TXT |
| GSE66177_akt_1_3.txt.gz |
14.3 Mb |
(ftp)(http) |
TXT |
| GSE66177_akt_1_4.txt.gz |
14.3 Mb |
(ftp)(http) |
TXT |
| GSE66177_akt_2_1.txt.gz |
14.4 Mb |
(ftp)(http) |
TXT |
| GSE66177_akt_2_2.txt.gz |
14.3 Mb |
(ftp)(http) |
TXT |
| GSE66177_akt_2_3.txt.gz |
14.3 Mb |
(ftp)(http) |
TXT |
| GSE66177_akt_2_4.txt.gz |
14.3 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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