Fra-1 enhances the radioresistance of colon cancer cells to X-ray or C-ion radiation

Abstract

Fos-related antigen 1 (Fra-1) has roles in a variety of cell functions, including cell proliferation, differentiation, transformation, and invasiveness, and it is upregulated in various cancers. We investigated the role of Fra-1 in cellular radioresistance using cells of two human colorectal cancer cell lines, SW620 and SW480. We found that SW620 cells are more sensitive than SW480 cells at doses greater than 6 Gy for X-ray or 3 Gy for carbon-ion (C-ion) radiation. Fra-1 expression tended to be decreased by the radiation in a dose-dependent manner in both cell lines; of note, a greater reduction of Fra-1 expression was observed in SW620 cells, especially at 6 Gy of X-ray or 3 Gy of C-ion irradiation, than in SW480 cells, indicating a possible association between Fra-1 downregulation and cellular radiosensitivity. Knockdown of Fra-1 in SW480 cells significantly increased the radiosensitivity to X-ray or C-ion radiation. On the other hand, overexpression of Fra-1 in SW620 cells significantly enhanced the radioresistance to C-ion radiation, suggesting a role of Fra-1 in radioresistance. Furthermore, we found that downregulation of Fra-1 protein in irradiated SW620 cells was regulated via protein degradation through a proteasome-dependent pathway. Overall, our results indicate a role of Fra-1 in radioresistance to both X-ray and C-ion radiation for colorectal cancer cell lines.