%0 Journal Article
%A Vaillant, Catherine
%A Valdivieso, Paola
%A Nuciforo, Sandro
%A Kool, Marcel
%A Schwarzentruber-Schauerte, Alexandra
%A Méreau, Hélène
%A Cabuy, Erik
%A Lobrinus, Johannes A
%A Pfister, Stefan
%A Zuniga, Aimée
%A Frank, Stephan
%A Zeller, Rolf
%T Serpine2/PN-1 Is Required for Proliferative Expansion of Pre-Neoplastic Lesions and Malignant Progression to Medulloblastoma.
%J PLoS one
%V 10
%N 4
%@ 1932-6203
%C Lawrence, Kan.
%I PLoS
%M DKFZ-2017-03704
%P e0124870 -
%D 2015
%X Medulloblastomas are malignant childhood brain tumors that arise due to the aberrant activity of developmental pathways during postnatal cerebellar development and in adult humans. 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 (Ptch1∆/+) are a good model to study the alterations underlying medulloblastoma development as a consequence of aberrant Hedgehog pathway activity.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 and WNT subgroups. As siRNA-mediated lowering of SERPINE2/PN-1 in human medulloblastoma DAOY cells reduces cell proliferation, we analyzed its potential involvement in medulloblastoma development using the Ptch1∆/+ mouse model. In Ptch1∆/+ mice, medulloblastomas arise as a consequence of aberrant Hedgehog pathway activity. Genetic reduction of Serpine2/Pn-1 interferes with medulloblastoma development in Ptch1∆/+ mice, as  60
%K Hedgehog Proteins (NLM Chemicals)
%K PTCH protein, human (NLM Chemicals)
%K Patched Receptors (NLM Chemicals)
%K Patched-1 Receptor (NLM Chemicals)
%K Ptch1 protein, mouse (NLM Chemicals)
%K Receptors, Cell Surface (NLM Chemicals)
%K Serpin E2 (NLM Chemicals)
%K Matrix Metalloproteinase 9 (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:25901736
%2 pmc:PMC4406471
%R 10.1371/journal.pone.0124870
%U https://inrepo02.dkfz.de/record/127681