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Involvement of p53 and interleukin 3 in the up-regulation of CD95 (APO-1/Fas) by X-ray irradiation

Oncogene volume 19, pages 3647–3655 (2000)Cite this article

Abstract

Interleukin 3-dependent bone marrow and Ba/F3 cells present constitutive Fas expression. A dose dependent increase in Fas surface expression was induced in these cells by X-ray irradiation. Using primary cell cultures and established cell lines derived from p53-null mice (p53−/−), we demonstrated that the increase in Fas expression upon X-ray irradiation is dependent on the presence of at least one wild-type p53 allele. Fas induction by X-ray irradiation was negatively modulated by IL-3; an earlier Fas induction was observed in the absence of IL-3 or at low IL-3 concentrations. However, IL-3 withdrawal in non-irradiated cells did not induce an increase in Fas expression. X-ray irradiation of Ba/F3 cells induced the expression of functional Fas receptors. Therefore, in IL-3-dependent cells, IL-3 regulates the rate of Fas expression, which is correlated with the degree of apoptosis observed in X-irradiated cells. Finally, we demonstrate that IL-3 controls the degree of Fas expression induced by irradiation through a p53-mediated pathway.

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Acknowledgements

We wish to thank Mary KL Collins for critical reading of the manuscript, Pedro Lastres for FACS analysis and Juana Maria Lopez Vera for her technical assistance. We are also indebted to JA Garcia-Sanz for advice and technical support. This work was supported by a grant SAF970064 from the Comisión Interministerial de Ciencia y Tecnología, Spain.

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  1. Department of Immunology, Centro de Investigaciones Biológicas (CIB-CSIC), Velázquez 144, Madrid, 28006, Spain

    A Gutiérrez del Arroyo, C Gil-Lamagniere, I Lazaro, M C de Marco, I Layunta & A Silva

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  1. A Gutiérrez del Arroyo
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Gutiérrez del Arroyo, A., Gil-Lamagniere, C., Lazaro, I. et al. Involvement of p53 and interleukin 3 in the up-regulation of CD95 (APO-1/Fas) by X-ray irradiation. Oncogene 19, 3647–3655 (2000). https://doi.org/10.1038/sj.onc.1203662

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