Involvement of wild-type p53 in radiation-induced c-Jun N-terminal kinase activation in human thyroid cells

c-jun-N-terminal kinases (JNKs) play an important role in defense against e xternal stresses including ionizing radiation (IR). We have previously show n that sensitivity, to IR is influenced by p53 status in human thyroid cell s. In this study, we investigated the effect of p53 status on IR-induced JN K activation in human thyroid cells. Our results showed high basal JNK acti vity in the p53-null thyroid cancer cell line, FRO. In contrast, primary cu ltured thyroid cells (PT), which harbor wildtype p53, had low basal JNK act ivity. IR increased JNK activity in PT, however, no such increase was noted in FRO cells. Introduction of the wild-type p53 into FRO cells reduced JNK activity to a low basal level and rendered it responsive to IR. There was no difference in IR-induced ceramide production between PT and FRO cells. O ur results provide clear evidence that p53 status influences, directly or i ndirectly, radiation-induced JNK activation in human thyroid cells, suggest ing that a feedback or interaction pathway between p53 and JNK regulates ra diation-induced cell fate.