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Absence of major defects in non-homologous DNA end joining in human breast cancer cell lines

Oncogene volume 21, pages 5654–5659 (2002)Cite this article

Abstract

Structural abnormalities of chromosomes, including translocations and deletions, are extremely frequent in human cancer cells and particularly in breast cancer cells. One hypothesis to account for these alterations is a deficiency in the repair of DNA double-strand breaks (DSB). This repair process relies on two distinct pathways, homologous recombination (HR) and non-homologous DNA end joining (NHEJ). To investigate this latter pathway, we have studied the ability of cell-free extracts from a variety of human cells to rejoin different types of DSBs. The end joining activity of eleven sporadic breast cancer cell lines (BCCLs) was compared with that of control cells including primary human fibroblasts and cells harbouring a limited number of chromosome abnormalities. In vitro rejoining activity was not detected in extracts from MO59J DNA-PKcs-deficient cells and was strongly inhibited by wortmannin in control extracts. In contrast, most sporadic BCCLs and BRCA1 or BRCA2 deficient cells demonstrated similar efficiencies and accuracies of in vitro NHEJ than control cells. Only two BCCLs, SKBR3 and MDA-MB-453 exhibited decreased in vitro NHEJ. This study therefore indicates that a major defect in the NHEJ pathway is unlikely to account for the high number of chromosomes abnormalities observed in sporadic and hereditary BCCLs.

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Acknowledgements

We thank Lucien Cabanier for help in mass culture of cell lines. P Mérel was supported by the Association de Recherche contre le Cancer, P Pfeiffer by a fellowship of the Heisenberg programme of the Deutsche Forschungsgemeinschaft. This work was supported by grants from the Comité de Paris of the Ligue Nationale Contre le Cancer and from the Institut Curie (PIC Génétique et Biologie des Cancers du Sein).

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Authors and Affiliations

  1. Laboratoire de Pathologie Moléculaire des Cancers, INSERM U509, Institut Curie, 26 rue d'Ulm, Paris, Cedex 05, 75248, France

    Philippe Mérel, Alexandre Prieur & Olivier Delattre

  2. FB9, GenetikUniversitaet, GH Essen Universitaetsstr, Essen, 5D-45117, Germany

    Petra Pfeiffer

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  1. Philippe Mérel
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Correspondence to Olivier Delattre.

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Mérel, P., Prieur, A., Pfeiffer, P. et al. Absence of major defects in non-homologous DNA end joining in human breast cancer cell lines. Oncogene 21, 5654–5659 (2002). https://doi.org/10.1038/sj.onc.1205742

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