MYC expression promotes the proliferation of neural progenitor cells in culture and in vivo

Neoplasia. Jan-Feb 2002;4(1):32-9. doi: 10.1038/sj.neo.7900200.

Abstract

Primitive neuroectodermal tumors (PNETs) are pediatric brain tumors that result from defects in signaling molecules governing the growth and differentiation of neural progenitor cells. We used the RCAS-TVA system to study the growth effects of three genetic alterations implicated in human PNETs on a subset of neural progenitor cells that express the intermediate filament protein, nestin. The genetic alterations tested were: 1) overexpression of the cellular oncoprotein, MYC; 2) activation of transcription factor, beta-catenin; and 3) haploinsufficiency of Ptc, the hedgehog receptor gene. The RCAS-TVA system uses an avian retroviral vector, RCAS, to target gene expression to specific cell types in transgenic mice. To express exogenous genes in neural progenitor cells, we used Ntv-a mice. In these mice, the Nestin gene promoter drives expression of TVA, the cell surface receptor for the virus. Ectopic expression of MYC, but not activated beta-catenin, promoted the proliferation of neural progenitor cells in culture and in the cerebral leptomeninges in vivo. These effects were equally penetrant in mice with Ptc+/- and Ptc+/+ genetic backgrounds. Although overexpression of MYC is not sufficient to cause intraparenchymal tumors, it may facilitate PNET formation by sustaining the growth of undifferentiated progenitor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Gene Expression
  • Genetic Vectors
  • Immunoenzyme Techniques
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neuroectodermal Tumors, Primitive / genetics
  • Neuroectodermal Tumors, Primitive / metabolism
  • Neuroectodermal Tumors, Primitive / pathology*
  • Neurons / metabolism
  • Patched Receptors
  • Patched-1 Receptor
  • Proto-Oncogene Proteins c-myc / genetics*
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface
  • Stem Cells / metabolism
  • Trans-Activators*
  • Transfection
  • beta Catenin

Substances

  • CTNNB1 protein, mouse
  • Cytoskeletal Proteins
  • Membrane Proteins
  • Patched Receptors
  • Patched-1 Receptor
  • Proto-Oncogene Proteins c-myc
  • Ptch1 protein, mouse
  • RNA, Messenger
  • Receptors, Cell Surface
  • Trans-Activators
  • beta Catenin