Purpose: To find a new molecule that affects p53-dependent
radiosensitivity. Methods and Materials: A
mouse sarcoma cell line, QRsP(p53+/+), was used. From this
cell line, we established a radiosensitive clone and a
radioresistant one. Colony
assay, p53
gene transfer, a
luciferase assay for p53 and p21, animal transplantation experiment, and
DNA array analyses were performed. Results:
Microarray showed marked reduction of a
transcription factor,
ATF5, both in vitro and in vivo for the radiosensitive clone. Interestingly,
flow cytometric analysis demonstrated marked
apoptosis for the radiosensitive clone by p53
cloned adenovirus infection.
Luciferase reporter
assay revealed that
ATF5 suppressed the transactivational activity of p53 and p63. By
ATF5 gene transfer, the radiosensitive clone regained resistance to both ionizing-radiation and Ad-p53 infection-induced
cell death. Surprisingly, time-lapse
cell migration observation revealed greater cell motility for ATF5-transfected radiosensitive clone. Conclusions: It seems likely that
ATF5 is a potent
repressor of p53 and elevated expression of
ATF5 in a
tumor may relate to enhanced
malignant phenotypes, such as
radioresistance or greater cell motility.
