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Effects on normal fibroblasts and neuroblastoma cells of the activation of the p53 response by the nuclear export inhibitor leptomycin B

Oncogene volume 18, pages 7378–7386 (1999)Cite this article

Abstract

p53 tumour suppressor protein levels and p53-dependent transcriptional activity have been recently shown to increase in cells treated with leptomycin B (LMB), an inhibitor of nuclear export. Experiments presented here show that LMB treatment leads to growth arrest and a senescence-like phenotype in human normal fibroblast cultures. This effect is reversible after removal of the drug and further passage by trypsinization. Instead, LMB has a strong cytotoxic effect on human neuroblastoma cell lines even at nanomolar concentrations. In both these cell types the effects of LMB are attenuated when the activity of the endogenous wild type p53 protein is abrogated by overexpression of a dominant negative p53 mutant. We conclude that the induction of the p53 response by LMB plays an important role in the effects of this drug on cultured cells.

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Acknowledgements

We wish to thank Ian Ellis for his help in the culture of HNFs, Sakari Heitanen and Jean-Christophe Bourdon for proofreading of the manuscript. P Smart was recipient of a studentship from the Medical Research Campaign. S Laín and C Midgley are recipients of postdoctoral fellowships from the Cancer Research Campaign. B Vojtesek was partly supported by GA CR No.:312/99/1550. DP Lane is a Gibb fellow of the Cancer Research Campaign. This work was funded by the Cancer Research Campaign grants SP2059/0102 and SP060/0102.

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Authors and Affiliations

  1. Department of Biochemistry, CRC Cell Transformation Group, MSI/WTB Complex, University of Dundee, Dundee, DD1 5EH, UK

    David P Lane, Carol Midgley & Sonia Laín

  2. Department of Anatomy and Physiology, CRC Cell Structure Research Group, MSI/WTB Complex, University of Dundee, Dundee, DD1 5EH, UK

    Philip Smart & E Birgitte Lane

  3. Department of Cellular and Molecular Oncology, Masaryk Memorial Cancer Institute, Zluty Kopec 7, 656 53, Brno, Czech Republic

    Borek Vojtesek

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Smart, P., Lane, E., Lane, D. et al. Effects on normal fibroblasts and neuroblastoma cells of the activation of the p53 response by the nuclear export inhibitor leptomycin B. Oncogene 18, 7378–7386 (1999). https://doi.org/10.1038/sj.onc.1203260

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