MDM2 gene and radiobiological effect in tumors

Murine double minute 2 (MDM2) gene is a critical component of the responses to both ionizing and UV radiation. The level of MDM2 expression determines the extent to which radiation induces an increase in the activity of the p53 tumor suppressor. MDM2 acts as a survival factor in many cell types by limiting the apoptotic function of p53. In addition, expression of MDM2 is induced in response to DNA damage, and the resulting high levels of MDM2 protein are thought to shorten the length of the cell cycle arrest established by p53 in the radiation response. Increased levels of MDM2 appear to ensure that the activity of p53 returns to its low basal levels in surviving cells. Decreased levels of MDM2 sensitize cells to radiation. Thus, MDM2 is a potential target for therapeutic intervention because its inhibition may radiosensitize the subset of human tumors expressing wild-type p53 such that radiotherapy is more efficacious. (authors)