RESEARCH ARTICLE Serpine2/PN-1 Is Required for Proliferative Expansion of Pre-Neoplastic Lesions and Malignant Progression to Medulloblastoma

Background Medulloblastomas are malignant childhood brain tumors that arise due to the aberrant activ-ity of developmental pathways during postnatal cerebellar development and in adult hu-mans. Transcriptome analysis has identified four major medulloblastoma subgroups. One of them, the Sonic hedgehog (SHH) subgroup, is caused by aberrant Hedgehog signal transduction due to mutations in the Patched1 (PTCH1) receptor or downstream effectors. Mice carrying a Patched-1 null allele (Ptch1Δ/+) are a good model to study the alterations underlying medulloblastoma development as a consequence of aberrant Hedgehog pathway activity. Results Transcriptome analysis of human medulloblastomas shows that SERPINE2, also called Protease Nexin-1 (PN-1) is overexpressed in most medulloblastomas, in particular in the SHH andWNT subgroups. As siRNA-mediated lowering of SERPINE2/PN-1 in human me-dulloblastoma DAOY cells reduces cell proliferation, we analyzed its potential involvemen