Hypoxia-induced down-modulation of PKCε promotes trail-mediated apoptosis of tumor cells

  • Authors:
    • Giuliana Gobbi
    • Elena Masselli
    • Cristina Micheloni
    • Antonio Nouvenne
    • Domenico Russo
    • Patrizia Santi
    • Alessandro Matteucci
    • Lucio Cocco
    • Marco Vitale
    • Prisco Mirandola
  • View Affiliations

  • Published online on: September 1, 2010     https://doi.org/10.3892/ijo_00000721
  • Pages: 719-729
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Abstract

Tumor oxygen status is considered as a prognostic marker that impacts on malignant progression and outcome of tumor therapy. TNF-related apoptosis inducing ligand (TRAIL) plays a key role in cancer immunity, with potential applications in cancer therapy. Protein kinase C (PKC)ε, a transforming oncogene, has a role in the protection of cardiomyocytes and neurons from hypoxia-induced damage while, it can also modulate the susceptibility of tumor cells to TRAIL-induced cell death. Here we demonstrate that hypoxia induces a tumor cell phenotype highly sensitive to the cytotoxic effects of TRAIL. Based on the observation that: i) PKCε expression levels are impaired during hypoxia, ii) the overexpression of PKCε, but not of a kinase-inactive PKCε mutant, is able to revert the hypoxia-induced sensitivity to TRAIL, iii) the down-modulation of PKCε levels by RNA interference, on the contrary, induces the highly TRAIL-sensitive phenotype, iv) the inhibition of hypoxia-inducible transcription factor-1α (HIF-1α) by specific siRNA blocks both the hypoxia-induced down-modulation of PKCε and the induction of the highly TRAIL-sensitive phenotype; we conclude that the HIF-1α upregulation during hypoxia is associated to PKCε down-modulation that likely represents the key molecular event promoting the apoptogenic effects of TRAIL in hypoxic tumor cells.

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September 2010
Volume 37 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Gobbi G, Masselli E, Micheloni C, Nouvenne A, Russo D, Santi P, Matteucci A, Cocco L, Vitale M, Mirandola P, Mirandola P, et al: Hypoxia-induced down-modulation of PKCε promotes trail-mediated apoptosis of tumor cells. Int J Oncol 37: 719-729, 2010
APA
Gobbi, G., Masselli, E., Micheloni, C., Nouvenne, A., Russo, D., Santi, P. ... Mirandola, P. (2010). Hypoxia-induced down-modulation of PKCε promotes trail-mediated apoptosis of tumor cells. International Journal of Oncology, 37, 719-729. https://doi.org/10.3892/ijo_00000721
MLA
Gobbi, G., Masselli, E., Micheloni, C., Nouvenne, A., Russo, D., Santi, P., Matteucci, A., Cocco, L., Vitale, M., Mirandola, P."Hypoxia-induced down-modulation of PKCε promotes trail-mediated apoptosis of tumor cells". International Journal of Oncology 37.3 (2010): 719-729.
Chicago
Gobbi, G., Masselli, E., Micheloni, C., Nouvenne, A., Russo, D., Santi, P., Matteucci, A., Cocco, L., Vitale, M., Mirandola, P."Hypoxia-induced down-modulation of PKCε promotes trail-mediated apoptosis of tumor cells". International Journal of Oncology 37, no. 3 (2010): 719-729. https://doi.org/10.3892/ijo_00000721