Restoration of FGF receptor type 2 enhances radiosensitivity of hormone-refractory human prostate carcinoma PC-3 cells.

ABSTRACT

BACKGROUND: This study was undertaken to investigate the radiosensitizing effects of fibroblast growth factor receptor 2IIIb (FGFR2IIIb) in androgen-independent human prostate carcinoma PC-3 cells devoid of normally resident epithelial cell FGFR2IIIb. MATERIALS AND METHODS: A clonal line of PC-3 cells expressing FGFR2IIIb was established by stable transfection. Clonogenic cell survival, apoptosis and cell cycle distribution with and without gamma-irradiation were then compared between FGFR2IIIb-expressing PC-3 cells and control cells mock-transfected with vector alone. RESULTS: Gamma-irradiation resulted in an increase of clonogenic cell death concurrent with enhanced apoptosis and cell cycle arrest in the G2/M-phase in both transfected and untransfected cells. A quantitative analysis of all three parameters indicated that cells expressing FGFR2IIIb were significantly more sensitive to irradiation than control cells. CONCLUSION: These results indicate that restoration of FGFR2IIIb to PC-3 cells enhances their sensitivity to irradiation through acceleration of apoptosis and cell cycle arrest.