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Enhanced expression and activity of DNA polymerase β in human ovarian tumor cells: impact on sensitivity towards antitumor agents

Oncogene volume 20, pages 6181–6187 (2001)Cite this article

Abstract

DNA polymerase β, one of the most inaccurate DNA synthesizing enzymes, has been shown to confer genetic instability when up-regulated in cells, a situation found in several human cancers. Here, we demonstrated that enhanced activity and expression of this enzyme occur in the human ovarian tumor 2008/C13*5.25 cells, which are resistant to the antitumor agent cisplatin and hypersensitive to 6-thioguanine. We found that translesion synthesis across platinated DNA crosslinks as well as increased incorporation into DNA of 6-thioguanine took place in the 2008/C13*5.25 cells compared to the parental 2008 cells. Such features being molecular signatures of DNA polymerase β, these findings suggest that deregulation of its expression in cancer cells may contribute to the modulation of the response to antitumor treatments and therefore to tumor progression.

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Abbreviations

Pol:

DNA polymerase

BER:

base excision repair

NER:

nucleotide excision repair

Ara-CTP:

1-β-D-Arabinofuranosylcytosine-triphosphate

AZT-TP:

3′-azido-3′ deoxythymidine triphosphate

ddCTP:

2′,3′-dideoxycytidine-triphosphate

6-TG:

6-thioguanine.

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Acknowledgements

This work was supported by Association pour la Recherche contre le Cancer (grant N° 9469 to JS Hoffmann and N° 5446 to C Cazaux), Région Midi-Pyrénées (grant N° 99001081 to C Cazaux and N° 99009282 to JS Hoffmann), and grant CA78648 from the National Institutes of Health (to SB Howell).

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Author notes

  1. Valérie Bergoglio and Yvan Canitrot: V Bergoglio and Y Canitrot contributed equally to this study

Authors and Affiliations

  1. Institut de Pharmacologie et de Biologie Structurale, UMR CNRS 5089, 205 route de Narbonne, 31077, Toulouse cedex, France

    Valérie Bergoglio, Yvan Canitrot, Christophe Cazaux & Jean-Sébastien Hoffmann

  2. LRF Molecular Pharmacology Group, CRU, Medical School, Newcastle-Upon-Tyne, UK

    Linda Hogarth & Lynne Minto

  3. Department of Medicine and the Cancer Center, University of California at San Diego, La Jolla, CA 92093-0058, California, USA

    Stephen B Howell

Authors
  1. Valérie Bergoglio
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  2. Yvan Canitrot
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  3. Linda Hogarth
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  4. Lynne Minto
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  5. Stephen B Howell
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  6. Christophe Cazaux
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  7. Jean-Sébastien Hoffmann
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Correspondence to Christophe Cazaux or Jean-Sébastien Hoffmann.

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Bergoglio, V., Canitrot, Y., Hogarth, L. et al. Enhanced expression and activity of DNA polymerase β in human ovarian tumor cells: impact on sensitivity towards antitumor agents. Oncogene 20, 6181–6187 (2001). https://doi.org/10.1038/sj.onc.1204743

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