title: E2F1 in gliomas: a paradigm of oncogene addiction.
abstract: Cancer arises as a result of a stepwise accumulation of genetic changes. One of these changes, deregulation of the Rb/E2F1 pathway resulting from alterations in members of the pathway, is a hallmark of all human cancers. These mutations promote tumor development by deregulating the E2F family of transcription factors, which results in uncontrolled cell cycle progression. The E2F1 protein functions as a transcription factor that enhances cell proliferation by binding to the promoter region of several genes, including those that are involved in cell cycle regulatory activities and DNA replication. It is now becoming clear that the role of E2F1 in regulating transcription and cell growth is also highly dependent on the cellular context. This complexity is also evident from analyses of perturbations in E2F-modulated tumor development. For example, deregulated E2F1 expression can either promote or inhibit tumorigenesis depending on the nature of the other oncogenic mutations that are present. This explains the ability of E2F1 to behave as both an oncogene and tumor suppressor gene. Here we focus on reviewing the most recent evidence supporting the "addiction" of gliomas to this versatile transcription factor. We also consider the clinical relevance of this by examining the role of E2F1 as a prognosis factor and as a target for the development of novel strategies.
authors.affiliation: Department of Neuro-Oncology, Unit 1002, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Marta M
authors.initials: MM
authors.lastname: Alonso
authors.forename: Ramon
authors.initials: R
authors.lastname: Alemany
authors.forename: Juan
authors.initials: J
authors.lastname: Fueyo
authors.forename: Candelaria
authors.initials: C
authors.lastname: Gomez-Manzano
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics*; D050687:E2F1 Transcription Factor / Q000235:genetics*; D050703:E2F2 Transcription Factor / Q000235:genetics; D005910:Glioma / Q000235:genetics*; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D009154:Mutation; D009857:Oncogenes
chemical_list: D050687:E2F1 Transcription Factor; D050703:E2F2 Transcription Factor; C493761:E2F2 protein, human