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Multiple defects of cell cycle checkpoints in U937-ASPI3K, an U937 cell mutant stably expressing anti-sense ATM gene

J Zhou1, W Liu, L Sun

  • 1Department of Hematology, Tongji Hospital, Tongji Medical University, Wuhan 430030.

Journal of Tongji Medical University = Tong Ji Yi Ke Da Xue Xue Bao
|July 5, 2003
PubMed

Insights

Ataxia-telangiectasia mutated gene (ATM) knockout in U937-ASPI3K cells disrupted cell cycle checkpoints and DNA damage response. This ATM-deficient model offers insights into cancer therapy mechanisms.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • The Ataxia-telangiectasia mutated (ATM) gene is crucial for cell cycle checkpoints and apoptosis in response to DNA damage.
  • Targeting ATM in tumor cells may offer therapeutic benefits and elucidate cell death mechanisms.

Purpose of the Study:

  • To characterize cell cycle checkpoint profiles in U937-ASPI3K cells with endogenous ATM knockout.
  • To investigate the response of these cells to DNA damaging agents like 137Cs irradiation.

Main Methods:

  • U937-ASPI3K cells with ATM knockout were synchronized and exposed to 137Cs irradiation.
  • Cell cycle kinetics, p53/p21 protein levels, and kinase activity (CDK2, p34CDC2) were assessed.

Main Results:

  • U937-ASPI3K cells showed multiple defects in cell cycle checkpoints, failing to arrest upon irradiation.
  • The accumulation of p53/p21 protein and inhibition of CDK kinase activity were abolished in these cells.

Conclusions:

  • Stable expression of anti-sense PI3K cDNA in U937-ASPI3K cells completely abolished multiple cell cycle checkpoints.
  • This ATM-deficient cell line serves as a valuable model for studying DNA damage response pathways in cancer therapy.

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