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A human cell line that maintains telomeres in the absence of telomerase and of key markers of ALT

Oncogene volume 24, pages 7893–7901 (2005)Cite this article

Abstract

In human somatic cells proliferation results in telomere shortening due to the end replication problem and the absence of adequate levels of telomerase activity. The progressive loss of telomeric DNA has been associated with replicative senescence. Maintenance of telomere structure and function is, therefore, an essential requisite for cells that proliferate indefinitely. Human cells that have acquired the immortal phenotype mostly rely on telomerase to compensate for telomere shortening with cell division. However, a certain percentage of immortalized cell lines and human tumors maintain their telomeres by Alternative Lengthening of Telomeres (ALT), a mechanism not fully understood but apparently based on homologous recombination. Here, we report the isolation of an immortal human cell line that is derived from an ALT cell line but maintains telomeres in the absence of key features of ALT and of telomerase. The properties of these cells suggest that the identification of ALT cells may not be reliably based on known ALT markers. This finding is of relevance for discriminating between the mortal and immortal phenotype among telomerase-negative cells in vitro and in vivo, particularly in regard to the development of pharmacological approaches for cancer treatment based on telomerase inhibition.

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Acknowledgements

We thank Hera Der-Sarkissian for excellent technical assistance, Roger Reddel for critical comments on the manuscript, Dominique Broccoli for providing the TRF2 antibody and Melanie J Dobson for the gift of the sub-telomeric plasmids. This work was supported by the National Cancer Research Institute of Canada (SB), the Cancer Research Society and the Canadian Institute of Health (IAO-64655 to CA), and l'Association pour la Recherche contre le Cancer, France (Grant 3588 to JAL-V). MA Cerone was supported by a US Army Department of Defense Breast Cancer Research Program Award. C Autexier is a Chercheur-Boursier of the Fonds de Recherches en Santé du Quebec and the recipient of a Boehringer-Ingelheim (Canada) Inc. Young Investigator Award.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, McGill University, H3A 2B4, Quebec, Canada

    Maria A Cerone & Chantal Autexier

  2. Bloomfield Center for Research in Aging, Lady Davis Institute, Jewish General Hospital, Montreal, H3T 1E2, Quebec, Canada

    Maria A Cerone & Chantal Autexier

  3. Telomeres and Cancer Laboratory, Pavillion Trouillet-Rossignol, Institut Curie, 26 Rue d'Ulm, Paris, 75248, France

    J Arturo Londoño-Vallejo

  4. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, L8N 3Z5, Ontario, Canada

    Silvia Bacchetti

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  1. Maria A Cerone
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  2. Chantal Autexier
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  3. J Arturo Londoño-Vallejo
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  4. Silvia Bacchetti
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Correspondence to Silvia Bacchetti.

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Cerone, M., Autexier, C., Londoño-Vallejo, J. et al. A human cell line that maintains telomeres in the absence of telomerase and of key markers of ALT. Oncogene 24, 7893–7901 (2005). https://doi.org/10.1038/sj.onc.1208934

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