Inhibitor of differentiation 4 drives brain tumor-initiating cell genesis through cyclin E and notch signaling

HM Jeon, X Jin, JS Lee, SY Oh, YW Sohn… - Genes & …, 2008 - genesdev.cshlp.org
HM Jeon, X Jin, JS Lee, SY Oh, YW Sohn, HJ Park, KM Joo, WY Park, DH Nam, RA DePinho
Genes & development, 2008genesdev.cshlp.org
Cellular origins and genetic factors governing the genesis and maintenance of
glioblastomas (GBM) are not well understood. Here, we report a pathogenetic role of the
developmental regulator Id4 (inhibitor of differentiation 4) in GBM. In primary murine
Ink4a/Arf−/− astrocytes, and human glioma cells, we provide evidence that enforced Id4 can
drive malignant transformation by stimulating increased cyclin E to produce a
hyperproliferative profile and by increased Jagged1 expression with Notch1 activation to …
Cellular origins and genetic factors governing the genesis and maintenance of glioblastomas (GBM) are not well understood. Here, we report a pathogenetic role of the developmental regulator Id4 (inhibitor of differentiation 4) in GBM. In primary murine Ink4a/Arf−/− astrocytes, and human glioma cells, we provide evidence that enforced Id4 can drive malignant transformation by stimulating increased cyclin E to produce a hyperproliferative profile and by increased Jagged1 expression with Notch1 activation to drive astrocytes into a neural stem-like cell state. Thus, Id4 plays an integral role in the transformation of astrocytes via its combined actions on two-key cell cycle and differentiation regulatory molecules.
genesdev.cshlp.org