The role of PML in the nervous system and in the pathogenesis of neuroblastoma. (360G-Wellcome-089116_Z_09_Z)

We have found that expression of the tumour suppressor PML is frequently lost in both mouse and human neuroblastoma primary tumours. We have also shown that PML acts as a growth suppressor at the level of neural progenitor/stem cells during embryonic development. This suggests that PML loss could be instrumental in leading to uncontrolled proliferation and a block of maturation in neuroblasts. Our key goal is to determine the involvement of PML in the pathogenesis of neuroblastoma. To this end, we set the following objectives: i) to assess whether the loss of PML expression correlates with disease outcome; ii) to determine the effect of PML loss on tumour growth in a mouse model of neuroblastoma; iii) to understand the molecular mechanisms underlying the loss of PML expression in neuroblastoma; iv) to establish the effects of PML re-expression in explants from mouse tumours and derived cell lines.