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| Status |
Public on Sep 14, 2006 |
| Title |
Gene expression-based chemical genomics identifies rapamycin as a modulator of MCL-1 and glucocorticoid resistance |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Drug resistance remains a major obstacle to successful cancer treatment. Here we use a novel approach to identify rapamycin as a glucocorticoid resistance reversal agent. A database of drug-associated gene expression profiles was screened for molecules whose profile overlapped with a gene expression signature of glucocorticoid (GC) sensitivity/resistance in Acute Lymphoblastic Leukemia (ALL) cells. The screen indicated the mTOR inhibitor rapamycin profile matched the signature of GC-sensitivity. We thus tested the hypothesis that rapamycin would induce GC sensitivity in lymphoid malignancy cells, and found that it sensitized cells to glucocorticoid induced apoptosis via modulation of antiapoptotic MCL1. These data indicate that MCL1 is an important regulator of GC-induced apoptosis, and that the combination of rapamycin and glucocorticoids has potential utility in ALL. Furthermore this approach represents a novel strategy for identification of promising combination therapies for cancer.
Keywords: drug resistance comparison
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| Overall design |
primary acute lymphoblastic leukemia samples were determined to be sensitive or resistant to in vitro treatment with glucocorticoids. Samples were then hybrized to affymetrix microarrays
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| |
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| Citation(s) |
17010674 |
| |
| Submission date |
Sep 13, 2006 |
| Last update date |
Aug 10, 2018 |
| Contact name |
Scott A. Armstrong |
| E-mail(s) |
scott.armstrong@childrens.harvard.edu
|
| Phone |
617-919-2508
|
| Fax |
617-730-0934
|
| Organization name |
Children's Hospital
|
| Department |
Hematology/Oncology
|
| Street address |
1 Blackfan Circle
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL96 |
[HG-U133A] Affymetrix Human Genome U133A Array |
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| Samples (29)
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| This SubSeries is part of SuperSeries: |
| GSE5824 |
Identification of rapamycin as a glucocorticoid resistance reversal agent |
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| Relations |
| BioProject |
PRJNA104383 |
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