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A p53 dose-response relationship for sensitivity to DNA damage in isogenic teratocarcinoma cells

Oncogene volume 20, pages 2982–2986 (2001)Cite this article

Abstract

Teratocarcinomas are tumors that arise from primordial germ cells and are readily curable with DNA-damaging chemotherapeutic drugs. Teratocarcinoma cells ex vivo in tissue culture are also relatively chemosensitive and undergo apoptotic death in response to DNA damage. We have previously hypothesized that the observed sensitivity of this tumor type to DNA damage is related to high basal expression of wild-type p53 protein. We have now addressed this issue by characterizing the DNA damage response of isogenic teratocarcinoma cells that differ only in their level of expression of wild-type p53 protein. We find a clear p53 dose-response relationship in these cells for rapid apoptosis following DNA damage that correlates with diminished colony formation in clonogenic survival assays. These results suggest that strategies to increase basal wild-type p53 protein expression prior to treatment with DNA-damaging drugs may improve curability in other tumor types.

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Acknowledgements

We thank Dr Moshe Oren (Weizmann Institute) for the murine p53 genomic clone. This work was supported by a grant from the Foundation of the University of Medicine and Dentistry of New Jersey. SG Lutzker is a Pfizer Scholar.

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Authors and Affiliations

  1. Department of Medicine, Robert Wood Johnson Medical School, New Jersey, 08901, NJ, USA

    Stuart G Lutzker

  2. Department of Biochemistry, Robert Wood Johnson Medical School, New Jersey, 08901, NJ, USA

    Stuart G Lutzker

  3. Department of Genetics and Microbiology, Robert Wood Johnson Medical School, New Jersey, 08901, NJ, USA

    Derek R Taller

  4. The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, 08901, New Jersey, NJ, USA

    Stuart G Lutzker, Robin Mathew & Derek R Taller

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Lutzker, S., Mathew, R. & Taller, D. A p53 dose-response relationship for sensitivity to DNA damage in isogenic teratocarcinoma cells. Oncogene 20, 2982–2986 (2001). https://doi.org/10.1038/sj.onc.1204394

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