Synergy between PI3K/Akt and Raf/MEK/ERK Pathways in IGF-1R Mediated Cell Cycle Progression and Prevention of Apoptosis in Hematopoietic Cells
| Autor: | Linda S. Steelman, John G. Shelton, Edmond R. White, James A. McCubrey |
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| Rok vydání: | 2004 |
| Předmět: | |
| Zdroj: | Cell Cycle. 3:370-377 |
| ISSN: | 1551-4005 1538-4101 |
| Popis: | The insulin like growth factor-1 (IGF-1) receptor (R) induced PI3K/Akt signal transduction cascade has critical roles in prevention of apoptosis and regulation of cell cycle progression. Here, we discuss the effects of IGF-1R-mediated signal transduction on hematopoietic cells which normally require interleukin-3 (IL-3) for growth and prevention of apoptosis. Cytokine-dependent FDC-P1 hematopoietic cells were conditionally transformed to grow in response to overexpression of IGF-1R in the presence of IGF-1. When these cells were deprived of IL-3 or IGF-1 for 24 hrs, they exited the cell cycle, activated caspase 3 and underwent apoptosis. The effects of inhibitors which targeted the PI3K/Akt and Raf/MEK/ERK pathways were determined. When the cells were cultured with IGF-1 and either PI3K or MEK inhibitors, cell cycle progression and DNA synthesis were inhibited and caspase 3 activity and apoptosis were induced. Co-inhibition of both pathways synergized to prevent cell cycle progression, inhibit DNA synthes... |
| Databáze: | OpenAIRE |
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