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

Vivo C, Lecomte C, Levy F, Leroy K, Kirova Y, Renier A, Kheuang L, Piedbois P, Chopin D, Jaurand MC - Br. J. Cancer (2003)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: INSERM EMI 9909, Faculté de Médecine, Université Paris XII, Creteil, France.

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.

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Related in: MedlinePlus

p53 (A) and p21WAF1/CIP1 (B) protein expression in HMCLs after exposure to several doses of γ-radiation. At 24 h after irradiation, protein extracts were subjected to SDS-PAGE electrophoresis followed by immunoblot analysis with antibodies against the corresponding antigens. ECL detection. Densitometric analyses of p53 and p21WAF1/CIP1 expression are reported on the top of the corresponding bands as percentage of the amount of protein expressed in untreated cells.
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fig3: p53 (A) and p21WAF1/CIP1 (B) protein expression in HMCLs after exposure to several doses of γ-radiation. At 24 h after irradiation, protein extracts were subjected to SDS-PAGE electrophoresis followed by immunoblot analysis with antibodies against the corresponding antigens. ECL detection. Densitometric analyses of p53 and p21WAF1/CIP1 expression are reported on the top of the corresponding bands as percentage of the amount of protein expressed in untreated cells.

Mentions: HMCLs were treated according to the same protocol as for the cell cycle studies. Western blot analysis of cells exposed to different doses of radiation showed no evident modification in the expression of p53 protein in the majority of HMCLs 24 h after irradiation (Figure 3AFigure 3


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

Vivo C, Lecomte C, Levy F, Leroy K, Kirova Y, Renier A, Kheuang L, Piedbois P, Chopin D, Jaurand MC - Br. J. Cancer (2003)

p53 (A) and p21WAF1/CIP1 (B) protein expression in HMCLs after exposure to several doses of γ-radiation. At 24 h after irradiation, protein extracts were subjected to SDS-PAGE electrophoresis followed by immunoblot analysis with antibodies against the corresponding antigens. ECL detection. Densitometric analyses of p53 and p21WAF1/CIP1 expression are reported on the top of the corresponding bands as percentage of the amount of protein expressed in untreated cells.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747542&req=5

fig3: p53 (A) and p21WAF1/CIP1 (B) protein expression in HMCLs after exposure to several doses of γ-radiation. At 24 h after irradiation, protein extracts were subjected to SDS-PAGE electrophoresis followed by immunoblot analysis with antibodies against the corresponding antigens. ECL detection. Densitometric analyses of p53 and p21WAF1/CIP1 expression are reported on the top of the corresponding bands as percentage of the amount of protein expressed in untreated cells.
Mentions: HMCLs were treated according to the same protocol as for the cell cycle studies. Western blot analysis of cells exposed to different doses of radiation showed no evident modification in the expression of p53 protein in the majority of HMCLs 24 h after irradiation (Figure 3AFigure 3

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: INSERM EMI 9909, Faculté de Médecine, Université Paris XII, Creteil, France.

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.

Show MeSH
Related in: MedlinePlus