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  • Original Paper
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Transferrin ensures survival of ovarian carcinoma cells when apoptosis is induced by TNFα, FasL, TRAIL, or Myc

Oncogene volume 22, pages 8343–8355 (2003)Cite this article

Abstract

The activation of Myc induces apoptosis of human ovarian adenocarcinoma N.1 cells when serum factors are limited. However, the downstream mechanism that is triggered by Myc is unknown. Myc-activation and treatment with the proapoptotic ligands TNFα, FasL, and TRAIL induced H-ferritin expression under serum-deprived conditions. H-ferritin chelates intracellular iron and also intracellular iron sequestration by deferoxamine-induced apoptosis of N.1 cells. Supplementation of serum-free medium with holo-transferrin blocked apoptosis of N.1 cells that was induced by Myc-activation or by treatment with TNFα, FasL, and TRAIL, whereas apotransferrin did not prevent apoptosis. This suggests that intracellular iron depletion was a trigger for apoptosis and that transferrin-bound iron rescued N.1 cells. Furthermore, apoptosis of primary human ovarian carcinoma cells, which was induced by TNFα, FasL, and TRAIL, was also inhibited by holo-transferrin. The data suggest that Myc-activation, FasL, TNFα, and TRAIL disturbed cellular iron homeostasis, which triggered apoptosis of ovarian carcinoma cells and that transferrin iron ensured survival by re-establishing this homeostasis.

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Acknowledgements

We thank the donators for providing pBABE-puro plasmid-, Myc:ER- and H-ferritin cDNA (listed under ‘Materials’), and Anton Jäger for excellent technical assistance in preparing part of the figures. This work was supported by the Unruhe Privatstiftung, and in part by the Herzfelder'sche Familienstiftung and the Anton Dreher Gedächtnisstiftung (to GK).

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  1. Sandra Fassl and Christina Leisser: Both authors contributed equally

Authors and Affiliations

  1. Institute of Clinical Pathology, University of Vienna, Waehringer Guertel 18-20, Vienna, A-1090, Austria

    Sandra Fassl, Christina Leisser, Simone Huettenbrenner, Susanne Maier, Georg Rosenberger, Stephan Strasser, Michael Grusch, Gerhard Fuhrmann, Katharina Leuhuber, Doris Polgar, Josefine Stani, Brigitte Tichy & Georg Krupitza

  2. Institute of Zoology, University of Vienna, Althanstrasse 14, Vienna, A-1090, Austria

    Katharina Leuhuber

  3. Department of Gynaecology and Obstetrics University of Vienna, Waehringer Guertel 18-20, Vienna, A-1090, Austria

    Christine Nowotny

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Correspondence to Georg Krupitza.

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Fassl, S., Leisser, C., Huettenbrenner, S. et al. Transferrin ensures survival of ovarian carcinoma cells when apoptosis is induced by TNFα, FasL, TRAIL, or Myc. Oncogene 22, 8343–8355 (2003). https://doi.org/10.1038/sj.onc.1207047

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