Regulation and deregulation of G2 checkpoint proteins with cisplatin

Anticancer Res. Nov-Dec 1998;18(6A):4057-66.

Abstract

Background: The G2 checkpoint has a key role in the response to DNA damage. G2 arrest following DNA damage is associated with inactivation of the protein kinase cyclin B-cdc2. The role of changes in protein expression in enzyme inhibition is controversial.

Methods: Expression of cyclin B1, cdc2, cdc25c, total protein and DNA content were examined by flow cytometry in two lung cancer cell lines. Changes in protein expression were compared to cell cycle matched controls under conditions associated with and without G2 arrest.

Results: Total protein increased with G2 arrest and decreased with cell death. Changes in cdc2, cdc25c and p16 paralleled changes in total protein. A larger increase in cyclin B1 was seen which was due to cell cycle redistribution. Deregulation of cyclin B1 was seen with a sublethal dose of cisplatin.

Conclusions: Our results do not support the model that changes in expression of cyclin B1 or other checkpoint proteins mediate G2 arrest after cisplatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CDC2 Protein Kinase / genetics
  • Carcinoma, Non-Small-Cell Lung
  • Cell Cycle / drug effects
  • Cell Cycle / physiology*
  • Cell Cycle Proteins / genetics
  • Cisplatin / toxicity*
  • Cyclin B / genetics
  • Cyclin B1
  • DNA / genetics
  • DNA Damage*
  • Flow Cytometry
  • G2 Phase
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / physiology
  • Homeostasis / drug effects
  • Humans
  • Kinetics
  • L Cells
  • Lung Neoplasms
  • Mice
  • Phosphoprotein Phosphatases / genetics
  • Tumor Cells, Cultured
  • cdc25 Phosphatases

Substances

  • CCNB1 protein, human
  • Ccnb1 protein, mouse
  • Cell Cycle Proteins
  • Cyclin B
  • Cyclin B1
  • DNA
  • CDC2 Protein Kinase
  • Phosphoprotein Phosphatases
  • cdc25 Phosphatases
  • Cisplatin