MYC Expression Promotes the Proliferation of Neural Progenitor Cells in Culture and In Vivo

• Main Authors: Dan Fults, Carolyn Pedone, Chengkai Dai, Eric C. Holland
• Format: Article
• Language: English
• Published: Elsevier 2002-01-01
• Series: Neoplasia: An International Journal for Oncology Research
• Subjects: MYC; neural progenitor cells; PNET; PTC; RCAS-TVA
• Online Access: http://www.sciencedirect.com/science/article/pii/S1476558602800458
• ISSN: 1476-5586; 1522-8002

Primitive neuroectodermal tumors. (20PNETs) 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, β-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 β-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.