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

Cancer Cell International
F IanziniM A Mackey

Abstract

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). 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. 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.

References

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Citations

Oct 26, 2007·Cancer Chemotherapy and Pharmacology·Fumio SakashitaMitsuru Seishima
Oct 10, 2007·Apoptosis : an International Journal on Programmed Cell Death·Anna SkwarskaJerzy Konopa
May 22, 2010·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·David Eriksson, Torgny Stigbrand
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Jun 9, 2009·Journal of Cancer Research and Clinical Oncology·Daniella PfeiferXiao-Feng Sun
Nov 17, 2015·International Journal of Molecular Sciences·Byeong Mo KimYonggeun Hong
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Dec 13, 2016·International Journal of Molecular Sciences·Atul Ranjan, Tomoo Iwakuma
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Oct 8, 2013·Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-Head and Neck Surgery·Simon D CarrJohn Greenman
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Jun 19, 2021·Frontiers in Oncology·Thijs A van SchaikKhalid Shah

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Methods Mentioned

BETA
light microscopy

Software Mentioned

WinMDI

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