Related Experiment Videos
Inverse relationship between epidermal growth factor receptor expression and radiocurability of murine carcinomas
T Akimoto1, N R Hunter, L Buchmiller
1Department of Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Abstract:
The study investigated whether a relationship exists between the extent of epidermal growth factor receptor (EGFR) expression and in vivo radiocurability of murine tumors. EGFR expression was determined in nine carcinomas (four mammary carcinomas, designated MCa-4, MCa-29, MCa-35, and MCa-K; two squamous cell carcinomas, designated SCC-IV and SCC-VII; an ovarian adenocarcinoma, OCa-I; a hepatocarcinoma, HCa-I; and an adenosquamous carcinoma, ACa-SG) syngeneic to C3Hf/Kam mice using Western blot analysis. These tumors greatly differed in their radioresponse, assessed by TCD50 assay, and in their susceptibility to radiation-induced apoptosis. Likewise, the expression of EGFR greatly varied, by as much as 21-fold, and the magnitude of the EGFR expression positively correlated with increased tumor radioresistance. The levels of EGFR inversely correlated with radiation-induced apoptosis, suggesting that the lack of sensitivity to apoptosis induction was a major mechanism responsible for radioresistance of tumors with high EGFR. This correlation was highly significant only for wild-type p53 carcinomas. Radiation activated EGFR autophosphorylation and increased the activity of protein tyrosine kinase, but only in tumors with high EGFR expression. Thus, EGFR expression was a major determinant of tumor radioresponse in vivo. The pretreatment assessment of EGFR expression could predict radiotherapy outcome and may assist in selecting an effective treatment modality.
Insights
High epidermal growth factor receptor (EGFR) expression in tumors correlates with increased radioresistance and reduced apoptosis. Pretreatment EGFR levels may predict radiotherapy outcomes, aiding treatment selection.
Area of Science:
- Oncology
- Radiation Oncology
- Molecular Biology
Background:
- Epidermal growth factor receptor (EGFR) is implicated in tumor growth and survival.
- Understanding factors influencing tumor response to radiation is crucial for effective cancer therapy.
Purpose of the Study:
- To investigate the relationship between epidermal growth factor receptor (EGFR) expression and the in vivo radiocurability of murine tumors.
- To determine if EGFR levels can predict tumor response to radiotherapy.
Main Methods:
- Western blot analysis was used to quantify EGFR expression in nine different murine carcinoma models.
- Tumor radioresponse was assessed using the TCD50 assay.
- Susceptibility to radiation-induced apoptosis was evaluated.
Main Results:
- EGFR expression varied significantly across the tested tumors (up to 21-fold).
- Higher EGFR expression positively correlated with increased tumor radioresistance and inversely with radiation-induced apoptosis.
- Radiation activated EGFR signaling (autophosphorylation and protein tyrosine kinase activity) in tumors with high EGFR expression.
Conclusions:
- EGFR expression is a significant determinant of in vivo tumor radioresponse.
- Tumor radioresistance in high-EGFR tumors is partly mediated by reduced sensitivity to apoptosis.
- Pretreatment EGFR assessment may help predict radiotherapy outcomes and guide treatment choices.