Cell cycle checkpoint status in human malignant mesothelioma cell lines: response to gamma radiation
| Autor: | F Levy, P Piedbois, Claire Vivo, Y Kirova, Karen Leroy, M C Jaurand, C Lecomte, Dominique Chopin, Laurence Kheuang, Annie Renier |
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| Rok vydání: | 2003 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Mesothelioma Cancer Research Cell cycle checkpoint Tumor suppressor gene Cell Simian virus 40 Biology Gene mutation Flow cytometry Cyclins Tumor Cells Cultured medicine Humans Cell Cycle Protein Cyclin medicine.diagnostic_test Cell Cycle Molecular and Cellular Pathology γ-radiation Cell cycle Genes cdc medicine.anatomical_structure Oncology mesothelioma cells cell cycle arrest Gamma Rays Mutation Immunology Cancer research Tumor Suppressor Protein p53 |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/sj.bjc.6600736 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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