Radiation-induced expression of functional Fas ligand in EBV-positive human nasopharyngeal carcinoma cells
โ Scribed by Bassam Abdulkarim; Siham Sabri; Eric Deutsch; Sabine Vaganay; Elisabetta Marangoni; William Vainchenker; Pierre Bongrand; Pierre Busson; Jean Bourhis
- Book ID
- 102650014
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- French
- Weight
- 519 KB
- Volume
- 86
- Category
- Article
- ISSN
- 0020-7136
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โฆ Synopsis
Ionizing radiation remains a major therapeutic tool against human cancers, especially epithelial tumors, which account for the majority of human malignancies. Although Fas and Fas-L are essential determinants of apoptosis, few data support their role in the cytotoxic effect of ionizing radiation. Epstein-Barr-virus (EBV)-positive nasopharyngeal carcinoma (NPC) were chosen to address this question owing to their known sensitivity to ionizing radiation and their constitutive expression of the Fas-receptor. We here report that, in xenografted NPC cells, Fas-L expression, which was very low in basal conditions, was dramatically increased by tumor irradiation. Both the Fas receptor and the Fas ligand were found to be functional in this model, and a high proportion of irradiated NPC cells underwent apoptosis following tumor irradiation. Induction of Fas-L expression and apoptosis were observed for doses as low as 2 Gy. These data show an increase in Fas-L expression upon irradiation exposure, and strongly suggest that, in some epithelial malignancies, Fasmediated apoptosis can play a major role in the anti-tumor effect of ionizing radiation, in the range of doses used for therapeutic applications.
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Fas (Apo-1, CD95), a member of the nerve growth factor/tumour necrosis factor receptor superfamily, mediates apoptosis in response to agonistic antibodies or Fas ligand (Fas-L) binding. Fas has been shown to be present on hepatocyte membranes in normal liver and in chronic hepatitis C. At the presen