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Updated: Jul 1, 2025

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p53/E2F7 axis promotes temozolomide chemoresistance in glioblastoma multiforme

Jiao Meng1,2, Wei Qian1,2,3, Zhenkun Yang1,2

  • 1Department of Laboratory Medicine, Wuxi People's Hospital, Wuxi Medical Center, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Nanjing Medical University, 214023, Wuxi, Jiangsu, China.

BMC Cancer
|March 8, 2024
PubMed
Abstract

Insights

High E2F7 expression, driven by p53, causes glioblastoma multiforme (GBM) chemoresistance by limiting drug uptake and DNA damage. This reveals a link between p53 activation and GBM treatment failure.

Area of Science:

  • Neuro-oncology
  • Cancer biology
  • Molecular mechanisms of cancer

Background:

  • Glioblastoma multiforme (GBM) is an aggressive brain cancer with poor prognosis.
  • Chemoresistance is a major challenge in treating GBM, with underlying mechanisms not fully understood.

Purpose of the Study:

  • To elucidate the mechanism of temozolomide (TMZ) resistance in GBM.
  • To investigate the role of E2F7 in GBM chemoresistance.

Main Methods:

  • Bioinformatics and antibody-based protein detection to analyze E2F7 expression in gliomas.
  • In vitro assays (IC50, viability, colony formation, apoptosis) and in vivo intracranial transplantation models to assess E2F7 function in TMZ resistance.
  • Western blot and ChIP experiments to confirm p53 regulation of E2F7.

Main Results:

  • Elevated E2F7 levels in GBM tissues correlated with poor patient prognosis.
  • E2F7 was upregulated in TMZ-resistant (TMZ-R) GBM, linked to reduced drug uptake and DNA damage.
  • p53 activation was identified as a regulator of E2F7 expression.

Conclusions:

  • High E2F7 expression, regulated by p53, confers TMZ resistance in GBM by impairing drug uptake and DNA damage.
  • Sustained p53 activation is significantly linked to GBM chemoresistance.
  • These findings suggest novel therapeutic strategies targeting the p53-E2F7 axis to overcome GBM chemoresistance.
Keywords:
ChemoresistanceE2F7Glioblastoma multiformeTemozolomidep53

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