Inverse relationship between epidermal growth factor receptor expression and radiocurability of murine carcinomas

The study investigated whether a relationship exists between the extent of epidermal growth factor receptor (EGFR) expression and in vivo radiocurabil ity of murine tumors. EGFR expression was determined in nine carcinomas (fo ur mammary carcinomas, designated MCa-4, MCa-29, MCa-35, and MCa-K; two squ amous cell carcinomas, designated SCC-IV and SCC-VIT; an ovarian adenocarci noma, OCa-I; a hepatocarcinoma, HCa-I; and an adenosquamous carcinoma, ACa- SG) syngeneic to C3Hf/Kam mice using Western blot analysis. These tumors gr eatly differed in their radioresponse, assessed by TCD50 assay, and in thei r susceptibility to radiation-induced apoptosis, Liken ise, the expression of EGFR greatly varied, by as much as 21-fold, and the magnitude of the EGF R expression positively correlated with increased tumor radioresistance, Th e levels of EGFR inversely correlated with radiation-induced apoptosis, sug gesting that the lack of sensitivity to apoptosis induction was a major mec hanism responsible for radioresistance of tumors with high EGFR. This corre lation was highly significant only for wild-type p53 carcinomas. Radiation activated EGFR autophosphorylation and increased the activity of protein ty rosine kinase, but only in tumors with high EGFR expression. Thus, EGFR exp ression was a major determinant of tumor radioresponse in vivo. The pretrea tment assessment of EGFR expression could predict radiotherapy outcome and may assist in selecting an effective treatment modality.