Abrogation of G1 arrest after DNA damage is associated with constitutive overexpression of Mdm2, Cdk4, and Irf1 mRNAs in the BALB/c 3T3 A31 variant 1-1 clone.
A search of cell lines showing aberrant cell-cycle checkpoints revealed the lack of gamma-irradiation-induced G1 arrest in the BALB/c 3T3 A31 variant 1-1 (A31-1-1) clone. This clone is well-known for its hypersensitivity to transformation by DNA damaging agents. p53 stabilization and p21 mRNA induction after 8 Gy irradiation were observed, suggesting that the abrogation of G1 arrest occurred in spite of normal p53 and p21 responses by abnormal regulation of other cellular factors. Constitutive overexpression of Mdm2 and Cdk4 mRNAs was found, which might have contributed to the loss of G1 arrest. In addition, overexpression of a growth-suppressive transcription factor, Irf1, a putative key molecule in the p53-independent pathway after DNA damage, was also observed, although the relation to the loss of G1 arrest could not be elucidated.
Nozaki
T
T
Department of Oral and Maxillo-Facial Surgery, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Japan. tnozaki@gan.ncc.go.jp
Masutani
M
M
Sugimura
T
T
Takato
T
T
Wakabayashi
K
K
D016475:3T3 Cells; D000818:Animals; D002999:Clone Cells; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000235:genetics*; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics*; D016193:G1 Phase; D050856:Interferon Regulatory Factor-1; D051379:Mice; D008807:Mice, Inbred BALB C; D009687:Nuclear Proteins; D010750:Phosphoproteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2; D012333:RNA, Messenger / Q000235:genetics
D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2; C495902:Cdk4 protein, mouse; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases