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PCTAIRE3: a putative mediator of growth arrest and death induced by CTS-1, a dominant-positive p53-derived synthetic tumor suppressor, in human malignant glioma cells

Cancer Gene Therapy volume 13, pages 469–478 (2006)Cite this article

Abstract

Chimeric tumor suppressor-1 (CTS-1) is based on the sequence of p53 and was designed as a therapeutic tool resisting various mechanisms of p53 inactivation. We previously reported that an adenovirus expressing CTS-1 (Ad-CTS-1) has superior cell death-inducing activity in glioma cells compared with wild-type p53. Here, we used cDNA microarrays to detect changes in gene expression preferentially induced by Ad-CTS-1. The putative serin threonine kinase, PCTAIRE3, and the quinone oxireductase, PIG3, were strongly induced by Ad-CTS-1 compared with wild-type p53. An adenoviral vector encoding PCTAIRE3 (Ad-PCTAIRE3) induced growth arrest and killed a minor proportion of the glioma cells. Ad-PIG3 alone affected neither growth nor viability. However, coinfection with Ad-PCTAIRE3 and Ad-PIG3 resulted in enhanced growth inhibition compared with Ad-PCTAIRE3 infection alone. Ad-CTS1, Ad-PCTAIRE3 or Ad-PIG3 induced the formation of free reactive oxygen species (ROS). However, the prevention of ROS formation induced by Ad-PCTAIRE3 and Ad-CTS-1 did not block growth arrest and cell death, suggesting that ROS formation is not essential for these effects. Altogether, these data identify PCTAIRE3 as one novel growth-inhibitory and death-inducing p53 response gene and suggest that changes in the expression of specific target genes contribute to the superior anti-glioma activity of CTS-1.

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Authors and Affiliations

  1. Department of General Neurology, Laboratory of Molecular Neuro-Oncology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany

    U Naumann, J Wischhusen, S Weit & M Weller

  2. International Agency for Research on Cancer (IARC), Lyon, France

    H Huang & H Ohgaki

  3. Institute of Pathology, University of Tübingen, Tübingen, Germany

    H Wolburg

Authors
  1. U Naumann
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  2. H Huang
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  3. H Wolburg
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  4. J Wischhusen
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  5. S Weit
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  6. H Ohgaki
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  7. M Weller
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Correspondence to U Naumann.

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Naumann, U., Huang, H., Wolburg, H. et al. PCTAIRE3: a putative mediator of growth arrest and death induced by CTS-1, a dominant-positive p53-derived synthetic tumor suppressor, in human malignant glioma cells. Cancer Gene Ther 13, 469–478 (2006). https://doi.org/10.1038/sj.cgt.7700917

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