ID3 mediates X-ray-induced apoptosis of keratinocytes through the regulation of β-catenin

Abstract

Background: Ionizing radiation is used to treat many of cancers, however, it also produces unwanted side effect on normal tissues, such as radiodermatitis. We previously established an animal model for radiodermatitis, and found that X-ray irradiation induced the expression of ID3 in hairless mouse skin by cDNA microarray.

Objective: The aim of this study is to investigate the functional role of ID3 in X-ray irradiated keratinocytes.

Methods: Immunohistochemistry, RT-PCR and Western blot were performed to demonstrate the ID3 induction by X-ray irradiation. HaCaT keratinocytes were transduced with the recombinant adenovirus expressing HA-ID3, and then effects on apoptosis were analyzed.

Results: X-ray irradiation increased markedly the ID3 protein level in epidermis of mouse skin. X-ray irradiation also induced the expression of ID3 in HaCaT keratinocytes cultured in vitro, at both mRNA and protein levels. When ID3 was overexpressed by recombinant adenovirus, apoptosis of keratinocytes were induced even in the absence of X-ray irradiation. Furthermore, overexpression of ID3 sensitized X-ray-induced apoptosis. Interestingly, X-ray irradiation significantly reduced the endogenous β-catenin level, which was related with induction of apoptosis. Similarly, overexpression of ID3 led to remarkable reduction in β-catenin level.

Conclusion: These results suggest that ID3 plays a role as an apoptosis inducer in response to X-ray irradiation via the regulation of endogenous β-catenin level.