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Loss of TP53 expression in immortalized choroid plexus epithelial cells results in increased resistance to anticancer agents

  • Laboratory Investigation
  • Published:
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Abstract

Choroid plexus carcinomas are malignant brain tumors predominantly arising in young children. Because a prognostic role of p53 alterations has been demonstrated, further research into potential underlying mechanisms is essential. Our objective was, therefore, to investigate the role of p53 in the growth-inhibitory potential of a variety of anticancer agents in the rodent choroid plexus epithelial cell line Z310. Furthermore, association of p53 alterations with proliferative activity (Ki67/MIB1) in choroid plexus carcinoma samples (N = 20) was examined by use of immunohistochemistry. Silencing of TP53 expression did not significantly alter metabolic activity in Z310 cells and p53 protein expression status was not associated with increased proliferative activity in choroid plexus carcinomas. However, the growth-inhibitory activity of vincristine, doxorubicin, carboplatin, etoposide, and temozolomide was significantly impaired by silencing of TP53. In conclusion, these results indicate a potential predictive role of p53 in choroid plexus carcinomas. Alterations of p53 should be taken into account when evaluating the effect of anticancer agents in future clinical trials.

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Acknowledgments

Birgit Lechtape, Susanne Peetz-Dienhart, Tanja Plagemann, and Barbara Riesmeier provided expert technical assistance. Supported by Deutsche Krebshilfe (DK 108263) and Innovative Medizinische Forschung (IMF).

Conflict of interest

The authors declare they have no conflict of interest.

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Authors and Affiliations

  1. Institute of Neuropathology, University Hospital Münster, Domagkstraße 19, 48149, Münster, Germany

    Miroslava Krzyzankova, Sonja Mertsch, Björn Koos, Astrid Jeibmann, Anne Kruse, Werner Paulus & Martin Hasselblatt

  2. Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Uwe Kordes

  3. Department of Pediatric Hematology and Oncology, Klinikum Augsburg, Augsburg, Germany

    Michael C. Frühwald

  4. Department of Pediatric Hematology and Oncology, University Hospital Münster, Münster, Germany

    Michael C. Frühwald

  5. Department of Pediatric Hematology Oncology, The Floating Hospital for Children, Tufts Medical Center, Boston, MA, USA

    Johannes E. Wolff

  6. Institute of Experimental Ophthalmology, University Eye Hospital Münster, Münster, Germany

    Sonja Mertsch

Authors
  1. Miroslava Krzyzankova
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  2. Sonja Mertsch
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  3. Björn Koos
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  4. Astrid Jeibmann
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  5. Anne Kruse
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  6. Uwe Kordes
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  7. Michael C. Frühwald
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  8. Johannes E. Wolff
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  9. Werner Paulus
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  10. Martin Hasselblatt
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Correspondence to Martin Hasselblatt.

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Krzyzankova, M., Mertsch, S., Koos, B. et al. Loss of TP53 expression in immortalized choroid plexus epithelial cells results in increased resistance to anticancer agents. J Neurooncol 109, 449–455 (2012). https://doi.org/10.1007/s11060-012-0915-3

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  • DOI: https://doi.org/10.1007/s11060-012-0915-3

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