Ectopic expression of Par-4 leads to induction of apoptosis in CNS tumor cell lines

  • Authors:
    • Susanne Vetterkind
    • Meike Boosen
    • Karl-Heinz Scheidtmann
    • Ute Preuss
  • View Affiliations

  • Published online on: January 1, 2005     https://doi.org/10.3892/ijo.26.1.159
  • Pages: 159-167
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Abstract

Prostate apoptosis response-4 (Par-4) is a pro-apoptotic protein originally identified as a gene product upregulated in prostate tumor cells undergoing apoptosis. Down-regulation of Par-4 has been linked to several cancers. Since Par-4 also plays a crucial role in neuronal apoptosis, we investigated the expression of Par-4 in tumor cell lines derived from representative tumor types of the CNS, including primitive neuroectodermal tumor (PNET), medulloblastoma, neuroblastoma and glioma of human, rat and murine origin. We show that Par-4 is frequently down-regulated, either transcriptionally or post-transcriptionally in the CNS tumor cell lines. Moreover, we demonstrate that ectopic expression of Par-4 is sufficient to directly induce apoptosis in these CNS tumor cells, in contrast to other cancer cells where replenishment of Par-4 levels only sensitizes the cells to apoptotic stimuli. Induction of apoptosis by Par-4 in the neural tumor cell lines is independent of endogenous Bcl-2 levels and PKCζ activity, although it has been proposed that Par-4 can exert its pro-apoptotic function by down-modulation of Bcl2 expression and inhibition of PKCζ. Co-expression of Par-4 and a dominant-negative mutant of FADD resulted in a slight reduction of apoptosis in some tumor cell lines, indicating that Par-4 may partially induce apoptosis via the Fas death pathway. Furthermore, these data suggested that the pro-apoptotic function of Par-4 involves (an)other yet unidentified apoptotic pathway(s) in the CNS tumor cell lines. Since Par-4 by itself is not sufficient to induce apoptosis in non-tumor cells, reintroduction of Par-4 into primary CNS tumors or reactivation of the pathways of Par-4-mediated apoptosis represent promising targets in anti-tumor therapy.

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January 2005
Volume 26 Issue 1

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

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APA
Vetterkind, S., Boosen, M., Scheidtmann, K., & Preuss, U. (2005). Ectopic expression of Par-4 leads to induction of apoptosis in CNS tumor cell lines. International Journal of Oncology, 26, 159-167. https://doi.org/10.3892/ijo.26.1.159
MLA
Vetterkind, S., Boosen, M., Scheidtmann, K., Preuss, U."Ectopic expression of Par-4 leads to induction of apoptosis in CNS tumor cell lines". International Journal of Oncology 26.1 (2005): 159-167.
Chicago
Vetterkind, S., Boosen, M., Scheidtmann, K., Preuss, U."Ectopic expression of Par-4 leads to induction of apoptosis in CNS tumor cell lines". International Journal of Oncology 26, no. 1 (2005): 159-167. https://doi.org/10.3892/ijo.26.1.159