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Tissue and cell-specific expression of the p53-target genes: bax, fas, mdm2 and waf1/p21, before and following ionising irradiation in mice

Oncogene volume 19, pages 649–660 (2000)Cite this article

Abstract

The mechanisms by which the p53 tumour suppressor protein would, in vivo, co-ordinate the adaptive response to genotoxic stress is poorly understood. p53 has been shown to transactivate several genes that could be involved in two main cellular responses, growth arrest and apoptosis. To get further insight into the tissue-specific regulation of p53 transcriptional activity, we performed an extensive study looking at the expression of four well characterized p53-responsive genes, before and after γ-irradiation in p53 wild-type (p53+/+) and p53-deficient (p53−/−) mice. The waf1, bax, fas and mdm2 genes were chosen for their different potential roles in the cellular response to stress. Our data demonstrate the strict p53-dependence of mRNA up-regulation for bax, fas and mdm2 in irradiated tissues and confirm such findings for waf1. They further highlight complex levels of regulatory mechanisms that could lead, in vivo, to selective transcriptional activation of genes by p53. In addition, our results provide arguments for the involvement of p53 in the basal mRNA expression of the four genes in some organs. Finally, in situ expression of Bax and p21Waf-1 protein suggests, at least in lymphoid organs, a direct correlation between selective p53-target gene expression and a particular response of a cell to ionising radiation.

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Acknowledgements

We wish to thank Lawrence D Donehower who generously provided us with the initial couple of p53 heterozygote mice. We are also most grateful to Hugh Brady, Moshe Oren and Shigekazu Nagata for kindly giving us the pCD2HAbaxα, pgemmusmdm2 and pVL1393BmuAPO constructs respectively. This work was supported by ARC and Electricité de France.

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  1. Tatiana Zaitchouk

    Present address: Department of Molecular Genetics (M/C 669), University of Illinois at Chicago, 900 South Ashland Av, Chicago, 60607, Illinois, IL, USA

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  1. Laboratoire de Cancérogenèse Moléculaire, UMR 217 CEA-CNRS, DRR, DSV, Centre d'Etude Nucleaire, CEA, 92265 Fontenay aux Roses Cedex, France

    Véronique Bouvard, Tatiana Zaitchouk, Monique Vacher, Arlette Duthu, Martine Canivet, Caroline Choisy-Rossi, Myriam Nieruchalski & Evelyne May

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Bouvard, V., Zaitchouk, T., Vacher, M. et al. Tissue and cell-specific expression of the p53-target genes: bax, fas, mdm2 and waf1/p21, before and following ionising irradiation in mice. Oncogene 19, 649–660 (2000). https://doi.org/10.1038/sj.onc.1203366

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