Gene expression-based chemical genomics identifies rapamycin as a modulator of MCL1 and glucocorticoid resistance
| Autor: | Jyoti Agarwal, David Twomey, Guo Wei, Stephen E. Sallan, Krysta D. Schlis, Justin Lamb, Ronald W. Stam, Todd R. Golub, Rob Pieters, Scott A. Armstrong, Joseph T. Opferman, Monique L. den Boer |
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| Přispěvatelé: | Pediatrics |
| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
Cell Survival Green Fluorescent Proteins Regulator Gene Expression CELLCYCLE Drug resistance Biology Dexamethasone Mice 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Databases Genetic Gene expression medicine Animals Humans MCL1 Glucocorticoids 030304 developmental biology Sirolimus 0303 health sciences Dose-Response Relationship Drug Cancer Genomics Cell Biology Precursor Cell Lymphoblastic Leukemia-Lymphoma Cell cycle medicine.disease Neoplasm Proteins 3. Good health Drug Combinations Proto-Oncogene Proteins c-bcl-2 Oncology Drug Resistance Neoplasm Apoptosis 030220 oncology & carcinogenesis Cancer research Myeloid Cell Leukemia Sequence 1 Protein Glucocorticoid medicine.drug |
| Zdroj: | Cancer Cell, 10, 1-12. Cell Press |
| ISSN: | 1535-6108 |
| Popis: | SummaryDrug resistance remains a major obstacle to successful cancer treatment. 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 that the mTOR inhibitor rapamycin profile matched the signature of GC sensitivity. We tested the hypothesis that rapamycin would induce GC sensitivity in lymphoid malignancy cells and found that it sensitized to GC-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 lymphoid malignancies. Furthermore, this approach represents a strategy for identification of promising combination therapies for cancer. |
| Databáze: | OpenAIRE |
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