E2F1 expression is deregulated and plays an oncogenic role in sporadic Burkitt's lymphoma.
Current treatments of sporadic Burkitt's lymphoma (sBL) are associated with severe toxicities. A better understanding of sBL formation would facilitate development of less toxic therapies. The etiology of sBL remains, however, largely unknown, C-MYC up-regulation being the only lesion known to occur in all sBL cases. Several studies examining the role of C-MYC in the pathogenesis of BL have concluded that C-MYC translocation is not the only critical event and that additional unidentified factors are expected to be involved in the formation of this tumor. We herein report that a gene distinct from C-MYC, E2F1, is involved in the formation of all or most sBL tumors. We found that E2F1 is highly expressed in Burkitt's lymphoma cell lines and sBL lymphoma specimens. Our data indicate that its elevated expression is not merely the consequence of the presence of more cycling cells in this tumor relative to other cell lines or to other neoplasias. In fact, we show that reduction of its expression in sBL cells inhibits tumor formation and decreases their proliferation rate. We also provide data suggesting that E2F1 collaborates with C-MYC in sBL formation. E2F1 expression down-regulation did not affect, however, the proliferation of human primary diploid fibroblasts. Because E2F1 is not needed for cell proliferation of normal cells, our results reveal E2F1 as a promising therapeutic target for sBL.
Molina-Privado
Irene
I
Instituto de Investigaciones Biomédicas de Madrid, Consejo Superior de Investigaciones Científicas, Hospital Gregorio Marañón, Madrid, Spain.
Rodríguez-Martínez
María
M
Rebollo
Patricia
P
Martín-Pérez
Daniel
D
Artiga
María-Jesús
MJ
Menárguez
Javier
J
Flemington
Erik K
EK
Piris
Miguel A
MA
Campanero
Miguel R
MR
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D001402:B-Lymphocytes / Q000378:metabolism / Q000502:physiology; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D050687:E2F1 Transcription Factor / Q000096:biosynthesis / Q000235:genetics*; D016195:G2 Phase / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D000199:Actins; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger