p53 isoform profiling in glioblastoma and injured brain.

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.

journal_name

Oncogene

journal_title

Oncogene

authors

Takahashi R,Giannini C,Sarkaria JN,Schroeder M,Rogers J,Mastroeni D,Scrable H

doi

10.1038/onc.2012.322

subject

Has Abstract

pub_date

2013-06-27 00:00:00

pages

3165-74

issue

26

eissn

0950-9232

issn

1476-5594

pii

onc2012322

journal_volume

32

pub_type

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