Format

Send to:

Choose Destination
See comment in PubMed Commons below
Genes Dev. 2008 Feb 15;22(4):436-48. doi: 10.1101/gad.1627008.

PI3K pathway regulates survival of cancer stem cells residing in the perivascular niche following radiation in medulloblastoma in vivo.

Author information

  • 1Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.

Abstract

Medulloblastomas are brain tumors that arise in the cerebellum of children and contain stem cells in a perivascular niche thought to give rise to recurrence following radiation. We used several mouse models of medulloblastomas in parallel to better understand how the critical cell types in these tumors respond to therapy. In our models, the proliferating cells in the tumor bulk undergo radiation-induced, p53-dependent apoptotic cell death. Activation of Akt signaling via PTEN loss transforms these cells to a nonproliferating extensive nodularity morphology. By contrast, the nestin-expressing perivascular stem cells survive radiation, activate PI3K/Akt pathway, undergo p53-dependent cell cycle arrest, and re-enter the cell cycle at 72 h. Furthermore, the ability of these cells to induce p53 is dependent on the presence of PTEN. These cellular characteristics are similar to human medulloblastomas. Finally, inhibition of Akt signaling sensitizes cells in the perivascular region to radiation-induced apoptosis.

PMID:
18281460
[PubMed - indexed for MEDLINE]
PMCID:
PMC2238666
Free PMC Article

Publication Types, MeSH Terms, Substances, Grant Support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk