title: E2F4 plays a key role in Burkitt lymphoma tumorigenesis.
abstract: Sporadic Burkitt lymphoma (sBL) is a rapidly growing B-cell non-Hodgkin's lymphoma whose treatment requires highly aggressive therapies that often result severely toxic. Identification of proteins whose expression or function is deregulated in sBL and play a role in its formation could facilitate development of less toxic therapies. We have previously shown that E2F1 expression is deregulated in sBL. We have now investigated the mechanisms underlying E2F1 deregulation and found that the E2F sites in its promoter fail to repress its transcriptional activity in BL cells and that the transcriptional repressor E2F4 barely interacts with these sites. We also have found that E2F4 protein levels, but not those of its mRNA, are reduced in sBL cell lines relative to immortal B-cell lines. E2F4 protein expression is also decreased in 24 of 26 sBL tumor samples from patients compared with control tissues. Our data demonstrate that enforced E2F4 expression in BL cells not only diminishes E2F1 levels, but also reduces selectively the tumorigenic properties and proliferation of BL cells, while increasing their accumulation in G(2)/M. Our results therefore point to E2F4 as a target for developing novel and less toxic treatments for sBL.
authors.affiliation: Department of Cancer Biology, Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Madrid, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Molina-Privado
authors.forename: R
authors.initials: R
authors.lastname: Jiménez-P
authors.forename: S
authors.initials: S
authors.lastname: Montes-Moreno
authors.forename: Y
authors.initials: Y
authors.lastname: Chiodo
authors.forename: M
authors.initials: M
authors.lastname: Rodríguez-Martínez
authors.forename: L
authors.initials: L
authors.lastname: Sánchez-Verde
authors.forename: T
authors.initials: T
authors.lastname: Iglesias
authors.forename: M A
authors.initials: MA
authors.lastname: Piris
authors.forename: M R
authors.initials: MR
authors.lastname: Campanero
mesh_terms: D000818:Animals; D002051:Burkitt Lymphoma / Q000737:chemistry / Q000209:etiology*; D002455:Cell Division; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000737:chemistry; D050719:Crk-Associated Substrate Protein / Q000502:physiology; D050687:E2F1 Transcription Factor / Q000032:analysis / Q000235:genetics; D050704:E2F4 Transcription Factor / Q000032:analysis / Q000502:physiology*; D005260:Female; D016195:G2 Phase; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic
chemical_list: C493841:BCAR1 protein, human; D050719:Crk-Associated Substrate Protein; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D050704:E2F4 Transcription Factor; C493762:E2F4 protein, human