Transgenic E2F1 expression in the mouse brain induces a human-like bimodal pattern of tumors

Melissa V. Olson, David G. Johnson, Hong Jiang, Jing Xu, Marta M. Alonso, Kenneth D. Aldape, Gregory N. Fuller, B. Nebiyou Bekele, W. K.Alfred Yung, Candelaria Gomez-Manzano, Juan Fueyo

Research output: Contribution to journalArticlepeer-review

Abstract

The Rb/E2F pathway is deregulated in most human brain tumors, and the finding that loss of E2F1 reduced pituitary tumorigenesis in Rb+/- mice suggests that loss of pRb induces brain tumors by activating E2F1. We therefore investigated the role of E2F1 in the development and maintenance of brain cancer using a transgenic mouse model engineered to express E2F1 specifically within glial cells (GFAP-tgE2F1). GFAP-tgE2F1 mice developed a highly penetrant phenotype characterized by neurologic defects, and examination of the brains revealed the presence of brain tumors in 20% of these animals. Importantly, the distribution of tumors according to mouse age suggests the existence of a bimodal pattern of tumor development, forcing a comparison with the human disease. Mice, at an early age, with deregulated E2F1 show the formation of embryonal brain tumors such as medulloblastoma, choroid plexus carcinoma, and primary neuroectodermal tumor. Conversely, at an older age, mice escaping embryonal tumor formation present with malignant gliomas, which are typically identified in the human adult population. Thus, this study offers the first evidence for a global role of E2F1 in the formation and maintenance of multilineage brain tumors, irrefutably establishing E2F1 as an oncogene in the brain.

Original languageEnglish (US)
Pages (from-to)4005-4009
Number of pages5
JournalCancer Research
Volume67
Issue number9
DOIs
StatePublished - May 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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