Up-regulation of Fas (CD95) in human p53wild-type cancer cells treated with ionizing radiation
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
9398058
DOI
10.1002/(sici)1097-0215(19971127)73:5<757::aid-ijc24>3.0.co;2-1
PII: 10.1002/(SICI)1097-0215(19971127)73:5<757::AID-IJC24>3.0.CO;2-1
Knihovny.cz E-resources
- MeSH
- fas Receptor metabolism MeSH
- Cell Cycle radiation effects MeSH
- Genes, p53 * MeSH
- Immunohistochemistry MeSH
- Humans MeSH
- Tumor Cells, Cultured radiation effects MeSH
- Tumor Suppressor Protein p53 metabolism MeSH
- Breast Neoplasms genetics metabolism pathology MeSH
- Up-Regulation radiation effects MeSH
- Dose-Response Relationship, Radiation MeSH
- Gamma Rays MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- fas Receptor MeSH
- Tumor Suppressor Protein p53 MeSH
Fas is a cell-surface protein which belongs to the tumor-necrosis-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 p53wild-type MCF-7 breast-carcinoma 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 G1 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 G1 and to up-regulate Fas after irradiation. In contrast, all 7 p53null and p53mutant lines failed not only to arrest their cell cycles in G1 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.
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