Up-regulation of Fas (CD95) in human p53wild-type cancer cells treated with ionizing radiation

✍ Scribed by Michael A. Sheard; Borek Vojtesek; Libuse Janakova; Jan Kovarik; Jan Zaloudik

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: French
• Weight: 231 KB
• Volume: 73
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19971127)73:5<757::aid-ijc24>3.0.co;2-1

✦ Synopsis

Fas is a cell-surface protein which belongs to the tumornecrosis-factor-receptor family. Signals through Fas are able to induce apoptosis in sensitive cells, and thus modalities for regulating the level of Fas expression on tumor cells are needed. We have studied cellular responses to gamma irradiation. The level of p53 tumor-suppressor protein was found to be elevated 3 hr after irradiation of p53 wild-type MCF-7 breastcarcinoma cells. Interestingly, accumulation of p53 was followed by up-regulation of surface Fas levels between 4 and 8 hr after irradiation. The level of Fas up-regulation was dependent on dose and, whereas elevation in the level of p53 was transient, enhancement of Fas expression was stable. Fas up-regulation occurred coincidentally with induction of G 1 cell-cycle arrest, a post-irradiation phenomenon known to be dependent on wild-type-p53 activity. We studied 9 other tumor lines, 2 with wild-type p53, 5 with mutant p53, and 2 expressing no p53. All lines expressing wild-type p53 were found to arrest in G 1 and to up-regulate Fas after irradiation. In contrast, all 7 p53 null and p53 mutant lines failed not only to arrest their cell cycles in G 1 phase, but also to up-regulate Fas levels in response to treatment. These findings demonstrate a direct correlation between wild-type-p53 activity and Fas up-regulation after treatment with ionizing radiation, strongly suggesting that post-irradiation Fas up-regulation is dependent on wild-type-p53 activity. Since low doses of radiation were sufficient to modulate Fas expression, up-regulation of the Fas death receptor may have clinical implications following radiotherapy.