Cell cycle checkpoint status in human malignant mesothelioma cell lines: response to gamma radiation

Our plain-English summary of Cell cycle checkpoint status in human malignant mesothelioma cell lines: response to gamma radiation, by C. Vivo, C. Lecomte, F. Levy, et al (British Journal of Cancer, 2003).

The study

• Authors: C. Vivo, C. Lecomte, F. Levy, K. Leroy, Y. Kirova, A. Renier, L. Kheuang, P. Piedbois, D. Chopin, M.C. Jaurand
• Journal: British Journal of Cancer
• Published: 2003;88(3):388-95
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

In plain English

This was a laboratory study of six cell lines grown from human malignant mesothelioma tumours, named RV, BT, BR, BL, CR and FR. It did not study asbestos exposure; asbestos appears only as background. The authors exposed the cells to gamma radiation at 6, 9 or 12 Gy. They measured whether the cells paused at two control points in their division cycle, called G1 and G2/M, and how the proteins p53, p21 and p27 changed. They also looked for mutations in the p53 gene and for the SV40 virus protein called T antigen. Four cell lines paused in G1. Two, RV and BT, did not pause in G1 but paused at G2/M instead. No apoptosis, a form of cell death, was seen. In the lines that paused in G1, p21 rose. SV40 T antigen was not found in any line. One line, BT, carried a p53 mutation at codon 248. The authors concluded that the lines responded differently, but all activated at least one checkpoint. They wrote that the lines appear resistant to DNA-damaging agents.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) experiment on human mesothelioma cell lines
• Who was studied: Six human malignant mesothelioma cell lines (RV, BT, BR, BL, CR and FR) obtained from confirmed mesothelioma cases and used between passages 3 and 15. The study was done in a laboratory in Créteil, France. Dates of the work and the tumour site are not given.
• Exposure: Gamma radiation at 6, 9 or 12 Gy from a cobalt-60 source. Asbestos exposure was not studied.
• Main results:
  • Two cell lines, RV and BT, did not arrest in G1 phase after irradiation, but arrested in G2/M phase. The G2/M increase was dose-dependent.
  • The other four cell lines arrested in G1 phase, with no apoptosis. BR arrested in G1 only. BL, CR and FR appeared to arrest in both G0/G1 and G2/M.
  • In the lines that failed to arrest in G1 (RV and BT), p21 was not induced. In the lines with G1 arrest, p21 expression was enhanced after irradiation.
  • Early after irradiation (0 to 6 hours), p53 protein rose in the cell lines that arrested in G1. The authors interpreted this as a transient stabilisation of p53.
  • SV40 T antigen DNA and RNA were not detected in any of the six cell lines, only in the positive control. No T antigen protein band was seen in any of the six lines.
  • One cell line, BT, had a p53 gene mutation at codon 248 (CGG to CAG), changing arginine to glutamine, with loss of the normal copy of the gene. The other five lines had a normal (wild-type) p53 gene.
• The authors' conclusion: The authors concluded that the cell lines responded differently to gamma radiation, but all activated cell cycle checkpoints in one or both phases. They wrote that the lines appear resistant to DNA-damaging agents. They suggested that therapies combining abrogation of cell cycle checkpoints with enhancement of cell death mechanisms should be investigated in mesothelioma.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Apoptosis, SV40.

Related studies

• Effect of simian virus large T antigen expression on cell cycle control and apoptosis in rat pleural mesothelial cells exposed to DNA damaging agents — V. Levresse, S. Moritz, et al. (1998)
• Analysis of cell cycle disruptions in cultures of rat pleural mesothelial cells exposed to asbestos fibers — V. Levresse, A. Renier, et al. (1997)
• SV40 and cell cycle perturbations in malignant mesothelioma — J.R. Testa, A. Giordano (2001)
• In vitro effects of recombinant human interferon gamma on human mesothelioma cell lines — L. Zeng, A. Buard, et al. (1993)
• Asbestos induction of extended lifespan in normal human mesothelial cells: interindividual susceptibility and SV40 T antigen — L. Xu, B.J. Flynn, et al. (1999)
• Accelerated cell cycle progression of human regulatory T cell-like cell line caused by continuous exposure to asbestos fibers — S. Lee, H. Matsuzaki, et al. (2017)

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