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Transcriptional Control and Deregulation, Signal Transduction and Cytokines

Human telomerase is regulated by erythropoietin and transforming growth factor-β in human erythroid progenitor cells

Leukemia volume 21, pages 2304–2310 (2007)Cite this article

Abstract

Telomerase catalytic subunit (hTERT) exerts important cellular functions including telomere homeostasis, genetic stability, cell survival and perhaps differentiation. However, the nature of external or internal signals, which regulate hTERT expression in tissues, remains poorly understood. Thus, whereas it has been described that hTERT gene is regulated along the differentiation of primitive myeloid progenitors, the effect of specific cytokines on telomerase expression in each myeloid lineage is currently unknown. Based on these considerations, we have investigated hTERT expression in erythroid cells treated with erythropoietin (EPO) and transforming growth factor β (TGFβ), as putative positive and negative regulators, respectively. We describe here that EPO activates hTERT gene transcription in in vitro-expanded primary erythroid precursors as well as in UT7 erythroleukemia cells. In UT7 cells, this study shows also that EPO acts through a JAK2/STAT5/c-myc axis. In contrast, TGFβ blocks EPO signaling downstream of c-myc induction through a Smad3-dependent mechanism. Finally, hTERT appears to be efficiently regulated by EPO and TGFβ in an opposite way in erythropoietic cells, arguing for a role of telomerase in red blood cell production.

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Acknowledgements

This work was supported by grants from the Institut National de la Santé et de la Recherche Médicale, the Association Laurette Fugain, the Association Cent pour Sang La Vie and the Fondation de France. NP-H was supported by a fellowship from the Ligue Nationale contre le Cancer. We are grateful to B Couderc for providing plasmids for retroviral infection. Thanks are due to Monique Laroche and Nicole Lhermie for technical assistance.

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Authors and Affiliations

  1. INSERM U563, Toulouse, France

    N Prade-Houdellier, E Frébet, C Demur, E-F Gautier, C Gaudin, G Laurent, V Mansat-De Mas & O Beyne-Rauzy

  2. Laboratoire d'Hématologie, CHU Purpan, Toulouse, France

    C Demur & V Mansat-De Mas

  3. INSERM U790, Villejuif, France

    F Delhommeau & A-L Bennaceur-Griscelli

  4. Faculté de Médecine Saint-Antoine, Université Pierre et Marie Curie-Paris 6, Paris, France

    F Delhommeau

  5. Département de la Biologie Clinique, Institut Gustave Roussy, Villejuif, France

    A-L Bennaceur-Griscelli

  6. Service d'Orthopédie, CHU Purpan, Toulouse, France

    V Martinel

  7. Service d'Hématologie, CHU Purpan, Toulouse, France

    G Laurent

  8. Université Toulouse III Paul Sabatier, Toulouse, France

    G Laurent, V Mansat-De Mas & O Beyne-Rauzy

  9. Service de Médecine Interne, CHU Purpan, Toulouse, France

    O Beyne-Rauzy

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  1. N Prade-Houdellier
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  9. G Laurent
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  11. O Beyne-Rauzy
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Correspondence to O Beyne-Rauzy.

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Prade-Houdellier, N., Frébet, E., Demur, C. et al. Human telomerase is regulated by erythropoietin and transforming growth factor-β in human erythroid progenitor cells. Leukemia 21, 2304–2310 (2007). https://doi.org/10.1038/sj.leu.2404874

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