E2F1 expression is deregulated and plays an oncogenic role in sporadic Burkitt's lymphoma.
E2F1 expression is deregulated and plays an oncogenic role in sporadic Burkitt's lymphoma.
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DOI：
10.1158/0008-5472.can-08-4617
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发表时间：
2009-05-01
期刊：
影响因子：
11.2
通讯作者：
Campanero MR
中科院分区：
文献类型：
--
作者：
Molina-Privado I;Rodríguez-Martínez M;Rebollo P;Martín-Pérez D;Artiga MJ;Menárguez J;Flemington EK;Piris MA;Campanero MR
目前sBL的治疗与严重毒性相关。更好地了解sBL的形成将有助于开发毒性较小的治疗方法。然而，散发性伯基特淋巴瘤（sBL）的病因在很大程度上仍然未知，因为C-MYC上调是已知在所有sBL病例中发生的唯一病变。几项研究检查了C-MYC在BL发病机制中的作用，得出的结论是C-MYC易位不是唯一的关键事件，预计其他未鉴定的因素也参与了这种肿瘤的形成。我们在此报告了一个与C-MYC不同的基因E2 F1参与了所有或大多数sBL肿瘤的形成。我们发现E2 F1在伯基特淋巴瘤细胞系和sBL淋巴瘤标本中高度表达。我们的数据表明，它的表达升高不仅仅是在这个肿瘤中相对于其他细胞系或其他瘤形成存在更多的循环细胞的结果。事实上，我们表明，减少其在sBL细胞中的表达可以抑制肿瘤形成并降低其增殖率。我们还提供了表明E2 F1与C-MYC在sBL形成中协作的数据。然而，E2 F1表达下调并不影响人原代二倍体成纤维细胞的增殖。由于正常细胞的细胞增殖不需要E2 F1，因此我们的结果表明E2 F1是sBL的有希望的治疗靶点。
Current treatments of sBL are associated with severe toxicities. A better understanding of sBL formation would facilitate development of less toxic therapies. The etiology of sporadic Burkitt’s lymphoma (sBL) remains however largely unknown, being C-MYC up-regulation 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, proliferation of human primary diploid fibroblasts. Since E2F1 is not needed for cell proliferation of normal cells, our results reveal E2F1 as a promising therapeutic target for sBL.