Journal article
Cytokine activation of phosphoinositide 3-kinase sensitizes hematopoietic cells to cisplatin-induced death
Cancer research (Chicago, Ill.), Vol.63(5), pp.1034-1039
2003
PMID: 12615719
Abstract
Cytokine growth factors regulate the normal proliferation of hematopoietic cells but can also override irradiation-induced growth arrest checkpoints through activation of a phosphoinositide 3-kinase (PI3K) signaling pathway. In the present study, we assessed the effect that erythropoietin and interleukin-3 have on cisplatin-treated hematopoietic cells. When cultured in the presence of cytokine, cisplatin-treated 32D cells transiently accumulated in a G(2)-M phase arrest and ultimately died by a nonapoptotic mechanism. By comparison, reduction of cytokine-induced PI3K activity, either through cytokine receptor mutation or direct inhibition with LY294002, caused cisplatin-treated cells to enter a biphasic G(1) and G(2)-M arrest. The arrest of these cells coincided with an absence of cyclin-dependent kinase (Cdk)1 and Cdk2 activity and significantly reduced cell death during cisplatin treatment. Indeed, LY294002 treatment during cisplatin exposure allowed the recovery of a viable, proliferating cell population after removal of cisplatin. In contrast, Cdks remained active in the G(2)-M-arrested population of cisplatin-treated cells with continuous cytokine activation of PI3K, and even transient exposure to cisplatin resulted in death of the entire population. These data suggest that cytokine activation of PI3K signaling pathways overrides cisplatin-induced growth arrest checkpoints, thereby sensitizing hematopoietic cells to DNA damage-induced death.
Details
- Title: Subtitle
- Cytokine activation of phosphoinositide 3-kinase sensitizes hematopoietic cells to cisplatin-induced death
- Creators
- Dipali NIMBALKAR - Department of Pharmacology, The University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, United StatesMatthew K HENRY - Department of Pharmacology, The University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, United StatesFrederick W QUELLE - Department of Pharmacology, The University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, United States
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.63(5), pp.1034-1039
- Publisher
- American Association for Cancer Research; Philadelphia, PA
- PMID
- 12615719
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Language
- English
- Date published
- 2003
- Academic Unit
- Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040317802771
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