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P53 plays a protective role against UV- and cisplatin-induced apoptosis in transcription-coupled repair proficient fibroblasts

Oncogene volume 20, pages 6805–6808 (2001)Cite this article

Abstract

We previously reported that transcription-coupled repair (TCR)-deficient human fibroblasts are extremely sensitive to UV-induced apoptosis and this sensitivity correlated with the induction of the p53 tumour suppressor. However, we have also found that p53 can be protective against UV-induced apoptosis. Thus, prior to this study, it was not clear whether the induction of p53 in TCR-deficient fibroblasts contributed to their death. To address this issue, we have expressed human papillomavirus E6 (HPV-E6) in primary fibroblasts derived from patients affected with xeroderma pigmentosum (complementation groups A, B and C) and Cockayne syndrome (complementation group B). We found that TCR-deficient (XP-A, XP-B and CS-B) fibroblasts were more sensitive than TCR-proficient cells (XP-C and normal) to both UV light and cisplatin treatment and this increase in sensitivity was not p53 dependent. Importantly, HPV-E6 expression increased the sensitivity of TCR-proficient normal and XP-C fibroblasts to UV- and cisplatin-induced apoptosis. This increase in sensitivity correlated with a decrease in the capacity of HPV-E6 expressing cells to recover mRNA synthesis following UV-irradiation. Therefore, we propose that p53 protects against UV- and cisplatin-induced apoptosis in a TCR-dependent manner and that p53 does not contribute strongly to the induction of apoptosis in TCR-deficient fibroblasts.

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Acknowledgements

We would like to thank Drs Christina Addison (Ottawa Regional Cancer Centre), Steve Ethier (University of Michigan), Denise Galloway (Fred Hutchinson Cancer Center), Doug Gray (Ottawa Regional Cancer Centre) and Theodore Lawrence (University of Michigan) for cell lines and viral constructs. We would also like to thank the staff at the flow cytometic core facility at the University of Michigan. This work was supported by a grant from the National Institutes of Health (CA82376-01) to M Ljungman and Cancer Care Ontario to BC McKay.

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  1. Centre for Cancer Therapeutics, Ottawa Regional Cancer Centre, Ottawa, K1H 8L6, Ontario, Canada

    Bruce C McKay & Cecilia Becerril

  2. Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109–0936, Michigan, USA

    Mats Ljungman

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  1. Bruce C McKay
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  2. Cecilia Becerril
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McKay, B., Becerril, C. & Ljungman, M. P53 plays a protective role against UV- and cisplatin-induced apoptosis in transcription-coupled repair proficient fibroblasts. Oncogene 20, 6805–6808 (2001). https://doi.org/10.1038/sj.onc.1204901

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