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p53 isoform profiling in glioblastoma and injured brain

Oncogene volume 32, pages 3165–3174 (2013)Cite this article

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Abstract

The tumor suppressor p53 has been found to be the most commonly mutated gene in human cancers; however, the frequency of p53 mutations varies from 10 to 70% across different cancer types. This variability can partly be explained by inactivating mechanisms aside from direct genomic polymorphisms. The p53 gene encodes 12 isoforms, some of which can modulate full-length p53 activity in cancer. In this study, we characterized p53 isoform expression patterns in glioblastoma, gliosis, non-tumor brain and neural progenitor cells by SDS–PAGE, immunoblot, mass spectrometry and reverse transcription–PCR. We found that the most consistently expressed isoform in glioblastoma, Δ40p53, was uniquely expressed in regenerative processes, such as those involving neural progenitor cells and gliosis compared with tumor samples. Isoform profiling of glioblastoma tissues revealed the presence of both Δ40p53 and full-length p53, neither of which were detected in non-tumor cerebral cortex. Upon xenograft propagation of tumors, p53 levels increased. The variability of overall p53 expression and relative levels of isoforms suggest fluctuations in subpopulations of cells with greater or lesser capacity for proliferation, which can change as the tumor evolves under different growth conditions.

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Acknowledgements

We would like to thank our Mayo Clinic colleagues for their contributions, in particular, Dr Robert Jenkins for seminal discussions on the etiology of GBM and xenograft biology; Alissa Caron for preparing GBM patient tumor specimens; Dr John Black for CTX samples; Guido Gonzalez for obtaining LNZ308 cells; and Benjamin Madden and the Mayo Clinic Protein Chemistry and Proteomics Shared Resource core for mass spectrometry analysis. We are grateful to past and current members of the Scrable lab for their enduring enthusiasm and abilities, in particular Dr Erica Ungewitter for her invaluable help with p53 antibodies and the work she did as a graduate student that laid the foundation for subsequent studies on p53 in ESCs, and Dr Silvia Medrano, for passing on her expertise with mouse NSC culture and the role of p53 in adult stem cells. This work was supported by PHS award R01AG026094 and a Senior Scholar in Aging award from the Ellison Medical Research Foundation to HS Additional support came from an NCI Cancer Center support grant to the Mayo Clinic Cancer Center, the Robert and Arlene Kogod Center on Aging at Mayo Clinic, the Mayo Brain Tumors SPORE, and the Mayo Clinic Medical Scientist Training Program (RT).

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Authors and Affiliations

  1. Medical Scientist Training Program, Mayo Clinic, Rochester, MN, USA

    R Takahashi

  2. Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA

    R Takahashi & H Scrable

  3. Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    C Giannini

  4. Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA

    J N Sarkaria & M Schroeder

  5. Banner Sun Health Research Institute, Sun City, AZ, USA

    J Rogers & D Mastroeni

  6. Division of Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    H Scrable

  7. Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA

    H Scrable

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Correspondence to H Scrable.

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Takahashi, R., Giannini, C., Sarkaria, J. et al. p53 isoform profiling in glioblastoma and injured brain. Oncogene 32, 3165–3174 (2013). https://doi.org/10.1038/onc.2012.322

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