P53 isoform profiling in glioblastoma and injured brain

R. Takahashi, C. Giannini, J. N. Sarkaria, M. Schroeder, J. Rogers, Diego Mastroeni, H. Scrable

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3165-3174
Number of pages10
JournalOncogene
Volume32
Issue number26
DOIs
StatePublished - Jun 27 2013
Externally publishedYes

Fingerprint

Glioblastoma
Protein Isoforms
Brain
Neoplasms
Gliosis
Stem Cells
p53 Genes
Mutation Rate
Heterografts
Cerebral Cortex
Reverse Transcription
Polyacrylamide Gel Electrophoresis
Mass Spectrometry
Polymerase Chain Reaction
Growth
Genes

Keywords

  • astrocytoma
  • gliosis
  • regeneration

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Takahashi, R., Giannini, C., Sarkaria, J. N., Schroeder, M., Rogers, J., Mastroeni, D., & Scrable, H. (2013). P53 isoform profiling in glioblastoma and injured brain. Oncogene, 32(26), 3165-3174. https://doi.org/10.1038/onc.2012.322

P53 isoform profiling in glioblastoma and injured brain. / Takahashi, R.; Giannini, C.; Sarkaria, J. N.; Schroeder, M.; Rogers, J.; Mastroeni, Diego; Scrable, H.

In: Oncogene, Vol. 32, No. 26, 27.06.2013, p. 3165-3174.

Research output: Contribution to journalArticle

Takahashi, R, Giannini, C, Sarkaria, JN, Schroeder, M, Rogers, J, Mastroeni, D & Scrable, H 2013, 'P53 isoform profiling in glioblastoma and injured brain', Oncogene, vol. 32, no. 26, pp. 3165-3174. https://doi.org/10.1038/onc.2012.322
Takahashi R, Giannini C, Sarkaria JN, Schroeder M, Rogers J, Mastroeni D et al. P53 isoform profiling in glioblastoma and injured brain. Oncogene. 2013 Jun 27;32(26):3165-3174. https://doi.org/10.1038/onc.2012.322
Takahashi, R. ; Giannini, C. ; Sarkaria, J. N. ; Schroeder, M. ; Rogers, J. ; Mastroeni, Diego ; Scrable, H. / P53 isoform profiling in glioblastoma and injured brain. In: Oncogene. 2013 ; Vol. 32, No. 26. pp. 3165-3174.
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