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Lack of p53 function promotes radiation-induced mitotic catastrophe in mouse embryonic fibroblast cells

BACKGROUND: We have demonstrated that in some human cancer cells both chronic mild heat and ionizing radiation exposures induce a transient block in S and G2 phases of the cell cycle. During this delay, cyclin B1 protein accumulates to supranormal levels, cyclin B1-dependent kinase is activated, and...

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Autores principales: Ianzini, Fiorenza, Bertoldo, Alessandro, Kosmacek, Elizabeth A, Phillips, Stacia L, Mackey, Michael A
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1479380/
https://www.ncbi.nlm.nih.gov/pubmed/16640786
http://dx.doi.org/10.1186/1475-2867-6-11
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author Ianzini, Fiorenza
Bertoldo, Alessandro
Kosmacek, Elizabeth A
Phillips, Stacia L
Mackey, Michael A
author_facet Ianzini, Fiorenza
Bertoldo, Alessandro
Kosmacek, Elizabeth A
Phillips, Stacia L
Mackey, Michael A
author_sort Ianzini, Fiorenza
collection PubMed
description BACKGROUND: We have demonstrated that in some human cancer cells both chronic mild heat and ionizing radiation exposures induce a transient block in S and G2 phases of the cell cycle. During this delay, cyclin B1 protein accumulates to supranormal levels, cyclin B1-dependent kinase is activated, and abrogation of the G2/M checkpoint control occurs resulting in mitotic catastrophe (MC). RESULTS: Using syngenic mouse embryonic fibroblasts (MEF) with wild-type or mutant p53, we now show that, while both cell lines exhibit delays in S/G2 phase post-irradiation, the mutant p53 cells show elevated levels of cyclin B1 followed by MC, while the wild-type p53 cells present both a lower accumulation of cyclin B1 and a lower frequency of MC. CONCLUSION: These results are in line with studies reporting the role of p53 as a post-transcriptional regulator of cyclin B1 protein and confirm that dysregulation of cyclin B1 promote radiation-induced MC. These findings might be exploited to design strategies to augment the yield of MC in tumor cells that are resistant to radiation-induced apoptosis.
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spelling pubmed-14793802006-06-15 Lack of p53 function promotes radiation-induced mitotic catastrophe in mouse embryonic fibroblast cells Ianzini, Fiorenza Bertoldo, Alessandro Kosmacek, Elizabeth A Phillips, Stacia L Mackey, Michael A Cancer Cell Int Primary Research BACKGROUND: We have demonstrated that in some human cancer cells both chronic mild heat and ionizing radiation exposures induce a transient block in S and G2 phases of the cell cycle. During this delay, cyclin B1 protein accumulates to supranormal levels, cyclin B1-dependent kinase is activated, and abrogation of the G2/M checkpoint control occurs resulting in mitotic catastrophe (MC). RESULTS: Using syngenic mouse embryonic fibroblasts (MEF) with wild-type or mutant p53, we now show that, while both cell lines exhibit delays in S/G2 phase post-irradiation, the mutant p53 cells show elevated levels of cyclin B1 followed by MC, while the wild-type p53 cells present both a lower accumulation of cyclin B1 and a lower frequency of MC. CONCLUSION: These results are in line with studies reporting the role of p53 as a post-transcriptional regulator of cyclin B1 protein and confirm that dysregulation of cyclin B1 promote radiation-induced MC. These findings might be exploited to design strategies to augment the yield of MC in tumor cells that are resistant to radiation-induced apoptosis. BioMed Central 2006-04-26 /pmc/articles/PMC1479380/ /pubmed/16640786 http://dx.doi.org/10.1186/1475-2867-6-11 Text en Copyright © 2006 Ianzini et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Primary Research
Ianzini, Fiorenza
Bertoldo, Alessandro
Kosmacek, Elizabeth A
Phillips, Stacia L
Mackey, Michael A
Lack of p53 function promotes radiation-induced mitotic catastrophe in mouse embryonic fibroblast cells
title Lack of p53 function promotes radiation-induced mitotic catastrophe in mouse embryonic fibroblast cells
title_full Lack of p53 function promotes radiation-induced mitotic catastrophe in mouse embryonic fibroblast cells
title_fullStr Lack of p53 function promotes radiation-induced mitotic catastrophe in mouse embryonic fibroblast cells
title_full_unstemmed Lack of p53 function promotes radiation-induced mitotic catastrophe in mouse embryonic fibroblast cells
title_short Lack of p53 function promotes radiation-induced mitotic catastrophe in mouse embryonic fibroblast cells
title_sort lack of p53 function promotes radiation-induced mitotic catastrophe in mouse embryonic fibroblast cells
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1479380/
https://www.ncbi.nlm.nih.gov/pubmed/16640786
http://dx.doi.org/10.1186/1475-2867-6-11
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