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Fibroblast growth factor-4 enhanced G2 arrest and cell survival following ionizing radiation
M Jung1, F G Kern, T J Jorgensen
1Department of Radiation Medicine, Vincent T. Lombardi Comprehensive Cancer Research Center, Georgetown University School of Medicine, Washington, DC 20007.
Abstract:
Fibroblast growth factors (FGFs) bind to cell membrane receptors and activate signal transduction pathways related to cell growth, angiogenesis, and tumorigenesis. FGFs have been shown to be abundantly expressed in some of the human tumors, which are known to be poorly responsive to radiation therapy. Using adrenal cortical carcinoma cells genetically engineered to express FGF-4, we have tested cellular survival following exposure to ionizing radiation. We report here that FGF-4 enhances cellular capacity to survive ionizing radiation. Furthermore, cell cycle analysis shows a pronounced increase in the duration of G2 arrest, suggesting perturbation of a cell cycle checkpoint. These findings implicate fibroblast growth factor-mediated signal transduction in cellular resistance of human tumors to radiation therapy.
Insights
Fibroblast growth factor-4 (FGF-4) enhances cancer cell survival after radiation exposure. This suggests FGF signaling contributes to tumor resistance to radiation therapy by altering cell cycle progression.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Fibroblast growth factors (FGFs) are implicated in cell growth, angiogenesis, and tumorigenesis.
- High FGF expression is observed in radioresistant human tumors.
- The role of FGFs in radiation resistance is not fully understood.
Purpose of the Study:
- To investigate the effect of FGF-4 on cellular survival following ionizing radiation.
- To determine the impact of FGF-4 on cell cycle progression in response to radiation.
Main Methods:
- Adrenal cortical carcinoma cells were genetically engineered to express FGF-4.
- Cells were exposed to ionizing radiation.
- Cellular survival assays were performed.
- Cell cycle analysis was conducted using flow cytometry.
Main Results:
- FGF-4 expression significantly enhanced the survival of cells exposed to ionizing radiation.
- Cell cycle analysis revealed a prolonged G2 arrest phase in FGF-4 expressing cells.
- This suggests FGF-4 perturbs cell cycle checkpoints.
Conclusions:
- FGF-4 confers enhanced radioresistance to cancer cells.
- FGF-mediated signal transduction plays a role in tumor resistance to radiation therapy.
- Targeting FGF signaling may represent a therapeutic strategy to overcome radioresistance.