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Updated: Aug 10, 2026
09:04
A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
Ionizing radiation modulates vascular endothelial growth factor (VEGF) expression through multiple mitogen activated
1Department of Radiation Oncology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia, VA 23298, USA.
Oncogene
|June 26, 2001
Summary
Ionizing radiation activates the MAPK pathway in glioblastoma cells, influencing proliferation, survival, and VEGF production. Inhibiting this pathway can enhance radiation
Area of Science:
- Molecular Biology
- Oncology
- Radiation Biology
Background:
- The mitogen-activated protein kinase (MAPK) pathway plays a crucial role in cellular responses to radiation.
- Vascular Endothelial Growth Factor (VEGF) is a key regulator of angiogenesis and tumor growth.
- Progression Elevated Gene 3 (PEG-3) is a radiation-responsive gene linked to VEGF production and tumorigenesis.
Purpose of the Study:
- To investigate the role of radiation-induced MAPK pathway activity in regulating proliferation, cell survival, and VEGF production in astrocytes and glioblastoma cells.
- To determine the impact of inhibiting MAPK signaling on radiation-induced apoptosis and cell growth.
- To elucidate the relationship between MAPK signaling, PEG-3, and VEGF expression in glioblastoma.
Main Methods:
- Treatment of primary astrocytes and glioblastoma cells (T9, RT2) with ionizing radiation (2 Gy).
- Pharmacological inhibition of the MAPK pathway using specific inhibitor drugs.
- Assessment of apoptosis, clonogenic cell survival, PEG-3 and VEGF promoter activity, and protein levels.
- Use of dominant-negative c-Jun (TAM67) to inhibit AP-1 transcription factor signaling.
Main Results:
- Ionizing radiation activated the MAPK pathway in all cell types, which was blocked by inhibitors.
- Inhibition of MAPK activity weakly enhanced radiation-induced apoptosis and reduced cell growth in RT2 cells.
- Radiation increased PEG-3 and VEGF promoter activity and protein levels in a MAPK-dependent manner.
- MAPK signaling and AP-1 transcription factor activity were found to regulate VEGF expression.
Conclusions:
- Radiation-induced MAPK signaling can promote cell survival and enhance the production of pro-angiogenic factors like VEGF.
- Inhibition of MAPK signaling may sensitize glioblastoma cells to radiation therapy by reducing proliferation and enhancing cell killing.
- MAPK and JNK pathway signaling converges on the AP-1 transcription factor to mediate enhanced VEGF expression in response to radiation.
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