Journal
CELL DEATH & DISEASE
Volume 1, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cddis.2010.28
Keywords
IGF1; p63; p53; radiation; cell cycle arrest; xerostomia
Categories
Funding
- NSF [NSF 0338247]
- NCI [T32 CA09213]
- NIDCR [K22 (DE16096), R01 (DE18888)]
Ask authors/readers for more resources
Radiotherapy for head and neck tumors often results in persistent loss of function in salivary glands. Patients suffering from impaired salivary function frequently terminate treatment prematurely because of reduced quality of life caused by malnutrition and other debilitating side-effects. It has been previously shown in mice expressing a constitutively active form of Akt (myr-Akt1), or in mice pretreated with IGF1, apoptosis is suppressed, which correlates with maintained salivary gland function measured by stimulated salivary flow. Induction of cell cycle arrest may be important for this protection by allowing cells time for DNA repair. We have observed increased accumulation of cells in G2/M at acute time-points after irradiation in parotid glands of mice receiving pretreatment with IGF1. As p21, a transcriptional target of the p53 family, is necessary for maintaining G2/M arrest, we analyzed the roles of p53 and p63 in modulating IGF1-stimulated p21 expression. Pretreatment with IGF1 reduces binding of Delta Np63 to the p21 promoter after irradiation, which coincides with increased p53 binding and sustained p21 transcription. Our data indicate a role for Delta Np63 in modulating p53-dependent gene expression and influencing whether a cell death or cell cycle arrest program is initiated. Cell Death and Disease (2010) 1, e50; doi:10.1038/cddis.2010.28; published online 10 June 2010
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available