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- Title
Involvement of p53 and Fas/CD95 in murine neural progenitor cell response to ionizing irradiation.
- Authors
Semont, Alexandra; Nowak, Ewa B; Lages, Céline Silva; Mathieu, Céline; Mouthon, Marc-André; May, Evelyne; Allemand, Isabelle; Millet, Pascal; Boussin, François D
- Abstract
We investigated the role of tumor suppressor p53 and Fas (CD95/APO-1), a member of the tumor necrosis factor receptor family, in neural progenitors response to?-irradiation exposure. Telencephalic cells were obtained from wild-type C57Bl/6, or p53-/-or fas-/-, 15-day-old mouse embryos. They were cultured in conditions allowing neural progenitors to form proliferating clusters (neurospheres). A 2?Gy?-irradiation induced a G1 cell cycle arrest and triggered apoptosis in wild-type neural progenitor cultures in correlation with an enhanced expression of p53 and of its downstream target p21WAF1, both of them acquiring a nuclear localization. These effects did not occur in p53-/-neural progenitors demonstrating the central role played by p53 in their response to ionizing radiation. Furthermore, the monoclonal antibody Jo2 directed against Fas induced apoptosis of wild type but not of fas-/-neural progenitors, indicating the existence of a functional Fas signaling pathway in neural progenitors. Ionizing radiation induced an increase of Fas membrane expression related to a p53-dependent increase of fas mRNA expression in wild-type neural progenitors. Moreover, fas-/-neural progenitors exhibited delayed radiation-induced apoptosis compared to wild-type cells. Therefore, these findings establish a role for Fas/CD95 related to p53 in the response of neural progenitors to?-radiation exposure. Similar mechanisms could be triggered in neural progenitors in case of different stresses during brain development or in the course of various diseases affecting the adult brain.Oncogene (2004) 23, 8497-8508. doi:10.1038/sj.onc.1207821 Published online 13 September 2004
- Subjects
P53 antioncogene; TUMOR necrosis factors; SUPPRESSOR cells; MESSENGER RNA; TUMORS; CELL cycle; IONIZING radiation
- Publication
Oncogene, 2004, Vol 23, Issue 52, p8497
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1207821