MYC expression promotes the proliferation of neural progenitor cells in culture and in vivo.
Brain, Brain-Neoplasms, Cytoskeletal-Proteins, Gene-Expression, Genetic-Vectors, Immunoenzyme-Techniques, Membrane-Proteins, Mice-Inbred-BALB-C, Mice-Inbred-C57BL, Mice-Transgenic, Neuroectodermal-Tumors-Primitive, Neurons, Proto-Oncogene-Proteins-c-myc, RNA-Messenger, Receptors-Cell-Surface, Stem-Cells, Trans-Activators, Transfection
Neoplasia 2002 Jan-Feb; 4(1):32-9.
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.
Fults, D; Pedone, C; Dai, C; and Holland, E C., "MYC expression promotes the proliferation of neural progenitor cells in culture and in vivo." (2002). Faculty Research 2000 - 2009. 919.