Driver or passenger effects of augmented c-Myc and Cdc20 in gliomagenesis

Ping Ji, Xinhui Zhou, Qun Liu, Gregory N. Fuller, Lynette M. Phillips, Wei Zhang

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Purpose: Cdc20 and c-Myc are commonly overexpressed in a broad spectrum of cancers, including glioblastoma (GBM). Despite this clear association, whether c-Myc and Cdc20 overexpression is a driver or passenger event in gliomagenesis remains unclear. Results: Both c-Myc and Cdc20 induced the proliferation of primary glial progenitor cells. c-Myc also promoted the formation of soft agar anchorage-independent colonies. In the RCAS/Ntv-a glia-specific transgenic mouse model, c-Myc increased the GBM incidence from 19.1% to 47.4% by 12 weeks of age when combined with kRas and Akt3 in Ntv-a INK4a-ARF (also known as CDKN2A)-null mice. In contrast, Cdc20 decreased the GBM incidence from 19.1% to 9.1%. Moreover, cell differentiation was modulated by c-Myc in kRas/Akt3-induced GBM on the basis of Nestin/GFAP expression (glial progenitor cell differentiation), while Cdc20 had no effect on primary glial progenitor cell differentiation. Materials and Methods: We used glial progenitor cells from Ntv-a newborn mice to evaluate the role of c-Myc and Cdc20 in the proliferation and transformation of GBM in vitro and in vivo. We further determined whether c-Myc and Cdc20 have a driver or passenger role in GBM development using kRas/Akt3 signals in a RCAS/ Ntv-a mouse model. Conclusions: These results suggest that the driver or passenger of oncogene signaling is dependent on cellular status. c-Myc is a driver when combined with kRas/Akt3 oncogenic signals in gliomagenesis, whereas Cdc20 overexpression is a passenger. Inhibition of cell differentiation of c-Myc may be a target for anti-glioma therapy.

Original languageEnglish (US)
Pages (from-to)23521-23529
Number of pages9
JournalOncotarget
Volume7
Issue number17
DOIs
StatePublished - Apr 26 2016

Keywords

  • Cdc20
  • Glial progenitor cell differentiation
  • Glioblastoma
  • Myc
  • RCAS/Ntv-a glia-specific mouse model

ASJC Scopus subject areas

  • Oncology

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