Multiple defects of cell cycle checkpoints in U937-ASPI3K, an U937 cell mutant stably expressing anti-sense ATM gene cDNA.
(Ataxia-telangiectasia mutated gene (ATM) functions in control of cell cycle checkpoints in responding to DNA damage and protects cells from undergoing apoptosis. Knock-out within tumor cells of endogenous ATM will achieve therapeutic benefits and enable a better understanding of the decisive mechanisms of cell death or survival in response to DNA damaging agents.) In present paper, we sought to characterize the cell cycle checkpoint profiles in U937-ASPI3K, a U937 cell mutant that was previously established with endogenous ATM knock-out phenotype. Synchronized U937-ASPI3K was exposed to 137Cs irradiation, G1, S, G2/M cell cycle checkpoint profiles were evaluated by determining cell cycle kinetics, p53/p21 protein, cyclin dependent kinase 2 (CDK2) and p34CDC2 kinase activity in response to irradiation. U937-ASPI3K exhibited multiple defects in cell cycle checkpoints as defined by failing to arrest cells upon irradiation. The accumulation of cellular p53/p21 protein and inhibition of CDK kinase was also abolished in U937-ASPI3K. It was concluded that the stable expression of anti-sense PI3K cDNA fragment completely abolished multiple cell cycle checkpoints in U937-ASPI3K, and hence U937-ASPI3K with an AT-like phenotype could serves as a valuable model system for investigating the signal transduction pathway in responding to DNA damaging-based cancer therapy.
Zhou
J
J
Department of Hematology, Tongji Hospital, Tongji Medical University, Wuhan 430030.
Liu
W
W
Sun
L
L
Sun
H
H
Tang
Y
Y
D017209:Apoptosis; D001260:Ataxia Telangiectasia / Q000235:genetics*; D064007:Ataxia Telangiectasia Mutated Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D004249:DNA Damage; D016373:DNA, Antisense / Q000096:biosynthesis* / Q000235:genetics; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins; D018816:Genes, cdc; D006801:Humans; D009154:Mutation; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics*; D025521:Tumor Suppressor Proteins; D020298:U937 Cells
D018797:Cell Cycle Proteins; D016373:DNA, Antisense; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases