Display Settings:

Format

Send to:

Choose Destination
Cancer Cell. 2012 May 15;21(5):601-13. doi: 10.1016/j.ccr.2012.04.012.

Distinct neural stem cell populations give rise to disparate brain tumors in response to N-MYC.

Author information

  • 1University of California, Department of Neurology, Brain Tumor Research Center and Helen Diller Family Comprehensive Cancer Center, San Francisco, CA 94158, USA. fredrik.swartling@igp.uu.se

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.

Copyright © 2012 Elsevier Inc. All rights reserved.

Comment in

PMID:
22624711
[PubMed - indexed for MEDLINE]
PMCID:
PMC3360885
Free PMC Article

Images from this publication.See all images (8)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8

Publication Types, MeSH Terms, Substances, Secondary Source ID, Grant Support

Publication Types

MeSH Terms

Substances

Secondary Source ID

Grant Support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk