TY - JOUR
T1 - Transgenic E2F1 expression in the mouse brain induces a human-like bimodal pattern of tumors
AU - Olson, Melissa V.
AU - Johnson, David G.
AU - Jiang, Hong
AU - Xu, Jing
AU - Alonso, Marta M.
AU - Aldape, Kenneth D.
AU - Fuller, Gregory N.
AU - Bekele, B. Nebiyou
AU - Yung, W. K.Alfred
AU - Gomez-Manzano, Candelaria
AU - Fueyo, Juan
PY - 2007/5/1
Y1 - 2007/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34249337114&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34249337114&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-06-2973
DO - 10.1158/0008-5472.CAN-06-2973
M3 - Article
C2 - 17483310
AN - SCOPUS:34249337114
SN - 0008-5472
VL - 67
SP - 4005
EP - 4009
JO - Cancer Research
JF - Cancer Research
IS - 9
ER -