Raised EGFR in combination with low cyclin D1 is associated with radioresistance in laryngeal carcinoma cells

Abstract

Introduction. Radiotherapy is one of the mainstays of treatment for squamous cell carcinoma. Identifying tumour markers able to predict tumour sensitivity to radiotherapy could enable patient/tumour specific treatment targeting and/or dose modification. In a recent study we demonstrated that high levels of EGFR and cyclin D1 were associated with disease recurrence after radiotherapy for patients with T2 laryngeal cancer.1 The aim of this study was to investigate this relationship in a panel of cell lines derived from laryngeal squamous cell carcinomas (LSCC). Methods. Six LSCC cell lines were exposed to 2Gy of gamma irradiation from a 147Caesium source. Following irradiation, a clonogenic assay was used to define the relative radiosensitivity (SF2) of each cell line. Western blot analysis, followed by densitometry measurement, was used to determine the relative expression of EGFR and cyclin D1 in each cell line. Results. Levels of EGFR and cyclin D1 were individually not strongly predictive for radiosensitivity. However, cell lines with a combination of high expression of EGFR and low expression of cyclin D1 were found to correlate strongly with a radioresistant phenotype (P = 0.95). Conclusions. This study accords with previous evidence that the cyclin D1/ EGFR axis is important in determining radiation susceptibility. However, in contrast to previous work we found that low, as opposed to high levels of cyclin D1, were associated with radioresistance. Our studies provide an opportunity for functional investigation of the roles of EGFR and cyclin D1 in determining radioresistance in LSCC cells.