MDM2 gene and radiobiological effect in tumors

Murine double minute 2 (MDM2) gene is a eritieal eomponent of the responses to both ionizing and UV radiation. The level of MDM2 expression determines the extent to whieh radiation induees an inerease in the aetivity of the p53 tumor suppressor. MDM2 aets as a survival faetor in many eell types by limiting the apoptotie funetion of p53. In addition, expression of MDM2 is indueed in response to DNA damage, and the resulting high levels of MDM2 protein are thought to shorten the length of the eell eyele arrest established by p53 in the radiation response. Inereased levels of MDM2 appear to ensure that the aetivity of p53 returns to its low basal levels in surviving eells. Deereased levels of MDM2 sensitize eells to radiation. Thus, MDM2 is a potential target for therapeutie intervention beeause its inhibition may radiosensitize the subset of human tumors expressing wild-type p53 sueh that radiotherapy is more efficaeious.