| Literature DB >> 22624711 |
Fredrik J Swartling1, Vasil Savov2, Anders I Persson3, Justin Chen3, Christopher S Hackett3, Paul A Northcott4, Matthew R Grimmer3, Jasmine Lau3, Louis Chesler5, Arie Perry3, Joanna J Phillips3, Michael D Taylor4, William A Weiss6.
Abstract
The proto-oncogene MYCN is mis-expressed in various types of human brain tumors. To clarify how developmental and regional differences influence transformation, we transduced wild-type or mutationally stabilized murine N-myc(T58A) into neural stem cells (NSCs) from perinatal murine cerebellum, brain stem, and forebrain. Transplantation of N-myc(WT) NSCs was insufficient for tumor formation. N-myc(T58A) cerebellar and brain stem NSCs generated medulloblastoma/primitive neuroectodermal tumors, whereas forebrain NSCs developed diffuse glioma. Expression analyses distinguished tumors generated from these different regions, with tumors from embryonic versus postnatal cerebellar NSCs demonstrating Sonic Hedgehog (SHH) dependence and SHH independence, respectively. These differences were regulated in part by the transcription factor SOX9, activated in the SHH subclass of human medulloblastoma. Our results demonstrate context-dependent transformation of NSCs in response to a common oncogenic signal.Entities:
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Year: 2012 PMID： 22624711 PMCID： PMC3360885 DOI： 10.1016/j.ccr.2012.04.012
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743