Primary research

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

Fiorenza Ianzini¹ , Alessandro Bertoldo² , Elizabeth A Kosmacek² , Stacia L Phillips¹ and Michael A Mackey³

¹  Departments of Pathology, Radiation Oncology, and Biomedical Engineering, University of Iowa, Iowa City, IA 52242, USA

²  Department of Biomedical Engineering, University of Iowa, Iowa City, IA 52242, USA

³  Departments of Biomedical Engineering and Pathology, University of Iowa, Iowa City, IA 52242, USA

author email corresponding author email

Cancer Cell International 2006, 6:11doi:10.1186/1475-2867-6-11

Published:	26 April 2006

Abstract

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.