Cell cycle checkpoint status in human malignant mesothelioma cell lines: response to gamma radiation.
Knowledge of the function of the cell cycle checkpoints in tumour cells may be important to develop treatment strategies for human cancers. The protein p53 is an important factor that regulates cell cycle progression and apoptosis in response to drugs. In human malignant mesothelioma, p53 is generally not mutated, but may be inactivated by SV40 early region T antigen (SV40 Tag). However, the function of p53 has not been investigated in mesothelioma cells. Here, we investigated the function of the cell cycle checkpoints in six human mesothelioma cell lines (HMCLs) by studying the cell distribution in the different phases of the cell cycle by flow cytometry, and expression of cell cycle proteins, p53, p21(WAF1/CIP1) and p27(KIP1). In addition, we studied p53 gene mutations and expression of SV40 Tag. After exposure to gamma-radiation, HMCLs were arrested either in one or both phases of the cell cycle, demonstrating a heterogeneity in cell cycle control. G1 arrest was p21(WAF1/CIP1)- and p53-dependent. Lack of arrest in G1 was not related to p53 mutation or binding to SV40 Tag, except in one HMCL presenting a missense mutation at codon 248. These results may help us to understand mesothelioma and develop new treatments.
Vivo
C
C
INSERM EMI 9909, Faculté de Médecine, Université Paris XII, Creteil, France.
Lecomte
C
C
Levy
F
F
Leroy
K
K
Kirova
Y
Y
Renier
A
A
Kheuang
L
L
Piedbois
P
P
Chopin
D
D
Jaurand
M C
MC
D002453:Cell Cycle / Q000528:radiation effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D005720:Gamma Rays; D018816:Genes, cdc / Q000528:radiation effects*; D006801:Humans; D008654:Mesothelioma / Q000473:pathology*; D009154:Mutation; D013539:Simian virus 40 / Q000235:genetics; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53