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Death receptor signaling regulatory function for telomerase: hTERT abolishes TRAIL-induced apoptosis, independently of telomere maintenance

Oncogene volume 23, pages 7469–7474 (2004)Cite this article

Abstract

Human telomerase has been implicated in cell immortalization and cancer. Recent works suggest that telomerase confers additional function required for tumorigenesis that does not depend on its ability to maintain telomeres. This new action may influence tumor therapy outcomes by yet unraveled mechanisms. Here, we show that overexpression of the catalytic subunit of telomerase (hTERT) protects a maturation-resistant acute promyelocytic leukemia (APL) cell line from apoptosis induced by the tumor necrosis factor (TNF) or TNF-related apoptosis-inducing ligand (TRAIL) and not from apoptosis induced by chemotherapeutic drugs such as etoposide or cisplatin. Conversely, in these cells, TRAIL-induced cell death is magnified by all-trans retinoic acid (ATRA) treatment, independently of telomerase activity on telomeres. Of note, this response is subordinated neither to maturation nor to telomere shortening. This work underlines that retinoids and death receptor signaling cross-talks offer new perspectives for antitumor therapy.

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Abbreviations

hTERT:

human telomerase reverse transcriptase

ATRA:

all-trans retinoic acid

GFP:

green fluorescent protein

TNF:

tumor necrosis factor

TRAIL:

TNF-related apoptosis-inducing ligand

DR:

death receptor

DAPI:

diamino-2-phenyl-indol

APL:

acute promyelocytic leukemia

TUNEL:

terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling

TRAP:

telomeric repeat amplification protocol

TA:

telomerase activity

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Acknowledgements

This work was supported by INSERM, the Ligue contre le Cancer, and Association pour la Recherche contre le Cancer (ARC nos. 4513 and 3416). FP and AS were funded by the Fondation pour la Recherche Médicale (FRM).

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  1. INSERM U496, Institut d'Hématologie, Hôpital Saint-Louis, 1, Avenue Claude Vellefaux, Paris, 75010, France

    Charles Dudognon, Frédéric Pendino, Josette Hillion, Anne Saumet, Michel Lanotte & Evelyne Ségal-Bendirdjian

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  1. Charles Dudognon
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  2. Frédéric Pendino
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Correspondence to Evelyne Ségal-Bendirdjian.

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Dudognon, C., Pendino, F., Hillion, J. et al. Death receptor signaling regulatory function for telomerase: hTERT abolishes TRAIL-induced apoptosis, independently of telomere maintenance. Oncogene 23, 7469–7474 (2004). https://doi.org/10.1038/sj.onc.1208029

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