c-Myc and β-catenin cooperate with loss of p53 to generate multiple members of the primitive neuroectodermal tumor family in mice Journal Article

Authors: Momota, H.; Shih, A. H.; Edgar, M. A.; Holland, E. C.
Article Title: c-Myc and β-catenin cooperate with loss of p53 to generate multiple members of the primitive neuroectodermal tumor family in mice
Abstract: Primitive neuroectodermal tumors (PNETs) are a family of primary malignant brain tumors that include medulloblastomas. Although genetic models of a subset of medulloblastomas are documented over the past decade, the molecular basis of other subclasses of PNET remains unclear. As elevated c-Myc expression, activation of Wnt/β-catenin signaling and dysfunction of p53 are seen in human PNETs, we investigated what role these abnormalities have in the formation of PNETs. Incorporating these abnormalities, we generated supratentorial PNET (sPNET) in mice using somatic cell gene transfer. We show that sPNETs arise from GFAP-expressing cells by forced c-Myc expression combined with p53 inactivation. β-catenin activation promotes tumor progression and induces divergent differentiation. These c-Myc+β-catenin-induced PNETs are histologically similar to large cell/anaplastic medulloblastomas and can occur in both cerebrum and cerebellum. Furthermore, we have obtained one PNET with marked epithelial differentiation having histological resemblance to choroid plexus carcinoma in this series. Our results in mice suggest that sPNET with varied differentiation and large cell/anaplastic medulloblastomas may be two tumor groups with similar genetic foundations. These data provide insights into the biology and classification of human PNETs and suggest that multiple tumor types or variants can be generated from a fixed set of genetic abnormalities. © 2008 Macmillan Publishers Limited All rights reserved.
Keywords: signal transduction; controlled study; protein expression; nonhuman; mouse; animals; mice; animal tissue; mus; somatic cell; glial fibrillary acidic protein; animal experiment; animal model; cell differentiation; protein p53; mice, inbred c57bl; gene transfer; mice, transgenic; myc protein; genes, myc; medulloblastoma; newborn; tumor suppressor protein p53; supratentorial neoplasms; gene inactivation; brain cancer; large cell carcinoma; epithelium; disease models, animal; c-myc; proto-oncogene proteins c-myc; beta catenin; neuroectoderm tumor; choroid plexus tumor; anaplastic carcinoma; p53; neuroectodermal tumors, primitive; primitive neuroectodermal tumor; mouse model; cerebellum tumor; b-catenin
Journal Title: Oncogene
Volume: 27
Issue: 32
ISSN: 0950-9232
Publisher: Nature Publishing Group  
Date Published: 2008-07-24
Start Page: 4392
End Page: 4401
Language: English
DOI: 10.1038/onc.2008.81
PUBMED: 18372915
PROVIDER: scopus
Notes: --- - "Cited By (since 1996): 12" - "Export Date: 17 November 2011" - "CODEN: ONCNE" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Hiroyuki Momota
    6 Momota
  2. Mark Allen Edgar
    45 Edgar
  3. Eric Holland
    224 Holland
  4. Alan H Shih
    56 Shih