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

Endo, Satoshi  ,  Fujita, Mayumi  ,  Yamada, Shigeru  ,  Imadome, Kaori  ,  Nakayama, Fumiaki  ,  ISOZAKI, TETSURO  ,  Yasuda, Takeshi  ,  Imai, Takashi  ,  Matsubara, Hisahiro

39 ( 3 )  , pp.1112 - 1118 , 2018-03 , Spandidos Publications
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.

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