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 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.


CONCLUSIONS
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.
Ianzini
Fiorenza
F
Department of Pathology, University of Iowa, Iowa City, IA 52242, USA. fiorenza-ianzini@uiowa.edu
Bertoldo
Alessandro
A
Kosmacek
Elizabeth A
EA
Phillips
Stacia L
SL
Mackey
Michael A
MA