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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 23, 2015 |
| Title |
Gene expression analysis of in vivo-grown tumors treated with compounds that either de-bulk the tumor or target cancer stem cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
A large body of evidence has demonstrated that many human tumors are maintained by a small cell population called cancer stem cells (CSCs) or tumor progenitors, which are responsible for tumor formation, therapy resistance and metastasis. We found that ionizing radiation treatment enriches for the CSC phenotype and properties by preferential survival and expansion of tumor progenitor cells. Our studies revealed that aldehyde dehydrogenase (ALDH) activity is indicative of prostate tumor progenitor cells with increased chemo- and radioresistance, enhanced migratory potential, improved DNA- double strand break repair and activation of the signaling pathways, which promote self-renewal and epithelial-mesenchymal transition. We found that X-ray irradiation can convert the bulk tumor cells to more clonogenic and radioresistant population positive for expression of CSC markers. For the first time we showed that irradiation increases histone H3K4 and H3K36 methylation in prostate cancer cells, thereby reactivating transcription of epigenetically silenced target genes. We showed that radioresistant tumor progenitor population undergoes a phenotypical switching during the course of irradiation, suggesting that controlling the phenotypical and functional properties of CSCs during radiation therapy is ultimative for the optimization of treatment strategies. Our studies have shown that CSC markers may be beneficial in prediction of tumor radiocurability, and combination of irradiation with therapies directed against CSCs can be a useful strategy to improve cancer treatment.
To identify potential biomarkers associated with CSC population in these xenograft tumors, we performed whole genome gene expression profiling of the xenograft tumors treated with NVP-BEZ235, which eliminates prostate cancer progenitor populations or with Taxotere, which targets the bulk tumor cells as compared with vehicle-treated control mice.
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| Overall design |
Treatment with either vehicle, Taxotere, NVP-BEZ235, or a combination of these two. There are no replicates
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| Contributor(s) |
Cojoc M, Peitzsch C, Kurth I, Trautmann F, Kunz-Schughart L, Telegeev GD, Stakhovsky EA, Walker JR, Simin K, Lyle S, Krause M, Baumann M, Dubrovska A |
| Citation(s) |
25670168 |
| Submission date |
Jul 25, 2013 |
| Last update date |
Mar 25, 2019 |
| Contact name |
John R Walker |
| E-mail(s) |
jwalker@gnf.org
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| Phone |
858-812-1636
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| Organization name |
Genomics Institute of the Novartis Research Foundation
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| Lab |
Genetics Core
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| Street address |
10675 John Jay Hopkins
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| City |
San Diego |
| State/province |
CA |
| ZIP/Postal code |
92121 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (4)
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| GSM1195690 |
DU145 xenograft in NOD/SCID mice_vehicle_4 weeks |
| GSM1195691 |
DU145 xenograft in NOD/SCID mice_taxotere_4 weeks |
| GSM1195692 |
DU145 xenograft in NOD/SCID mice_NVP-BEZ235_4 weeks |
| GSM1195693 |
DU145 xenograft in NOD/SCID mice_NVP-BEZ235 and taxotere_4 weeks |
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| Relations |
| BioProject |
PRJNA213323 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE49232_RAW.tar |
33.1 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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