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

• Published in: International journal of cancer Vol. 73; no. 5; pp. 757 - 762
• Main Authors: Sheard, Michael A., Vojtesek, Borek, Janakova, Libuse, Kovarik, Jan, Zaloudik, Jan
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 27.11.1997; Wiley-Liss
• Subjects: Biological and medical sciences; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Cycle - radiation effects; Dose-Response Relationship, Radiation; fas Receptor - metabolism; Female; Gamma Rays; Genes, p53; Humans; Immunohistochemistry; Medical sciences; Radiation therapy and radiosensitizing agent; Treatment with physical agents; Treatment. General aspects; Tumor Cells, Cultured - radiation effects; Tumor Suppressor Protein p53 - metabolism; Tumors; Up-Regulation - radiation effects; Human; Malignant tumor; Radiotherapy; In vitro; Cell surface; Dose activity relation; Antigen; Gamma irradiation; Regulation(control); TP53 Gene; Treatment; Established cell line; Tumor suppressor gene
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19971127)73:5<757::AID-IJC24>3.0.CO;2-1

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. Int. J. Cancer 73:757–762, 1997. © 1997 Wiley‐Liss, Inc.