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| Status |
Public on Dec 22, 2016 |
| Title |
Expression data from a triple-negative BRCA1-mutated ortho-xenograft treated with sirolimus |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.
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| Overall design |
A metastatic triple-negative BRCA1-mutated (germline) breast tumor orthotopically engrafted in nude mice was treated with sirolimus (5 mg/kg) or DMSO (control) for approximately 60 days. Subsequently, RNA was extracted, processed, and hybridized on Affymetrix microarrays.
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| Contributor(s) |
Aguilar H, Mateo F, Villanueva A, Pujana MA |
| Citation(s) |
27991928 |
| Submission date |
Jul 27, 2012 |
| Last update date |
Mar 21, 2019 |
| Contact name |
Miguel Angel Pujana |
| E-mail(s) |
mapujana@iconcologia.net
|
| Phone |
0034932607463
|
| Organization name |
Institut Catala d'Oncologia IDIBELL
|
| Lab |
ProCURE
|
| Street address |
Gran Via 199
|
| City |
Barcelona |
| ZIP/Postal code |
08908 |
| Country |
Spain |
| |
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| Platforms (1) |
| GPL13667 |
[HG-U219] Affymetrix Human Genome U219 Array |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE39694 |
Expression data from orthotopic tumors and the MCF7 and HCC1937 breast cancer cell lines |
|
| Relations |
| BioProject |
PRJNA171489 |
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