MYC expression promotes the proliferation of neural progenitor cells in culture and in vivo Journal Article
| Authors: | Fults, D.; Pedone, C.; Dai, C.; Holland, E. C. |
| Article Title: | MYC expression promotes the proliferation of neural progenitor cells in culture and in vivo |
| 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, 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. |
| Keywords: | signal transduction; promoter region; mutation; nonhuman; brain neoplasms; cell proliferation; animal cell; mouse; animals; mice; gene overexpression; gene expression; cell growth; sonic hedgehog protein; membrane proteins; cell differentiation; neurons; transfection; mice, inbred balb c; mice, inbred c57bl; genetic vectors; mice, transgenic; stem cell; immunoenzyme techniques; brain; rna, messenger; newborn; stem cells; trans-activators; proto-oncogene proteins c-myc; beta catenin; nestin; nerve cell culture; neuroectoderm tumor; neural progenitor cells; oncogene myc; neuroectodermal tumors, primitive; myc; cytoskeletal proteins; cell surface receptor; receptors, cell surface; pnet; priority journal; article; ptc; rcas-tva |
| Journal Title: | NeoPlasia |
| Volume: | 4 |
| Issue: | 1 |
| ISSN: | 1522-8002 |
| Publisher: | Elsevier Science Inc. |
| Date Published: | 2002-01-01 |
| Start Page: | 32 |
| End Page: | 39 |
| Language: | English |
| DOI: | 10.1038/sj/neo/7900200 |
| PUBMED: | 11922389 |
| PROVIDER: | scopus |
| PMCID: | PMC1503312 |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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