De Falco Giulia, Leucci Eleonora, Lenze Dido, Piccaluga Pier Paolo, Claudio Pier Paolo, Onnis Anna, Cerino Giovanna, Nyagol Joshua, Mwanda Walter, Bellan Cristiana, Hummel Michael, Pileri Stefano, Tosi Piero, Stein Harald, Giordano Antonio, Leoncini Lorenzo
Department of Human Pathology and Oncology, University of Siena, Italy.
Blood. 2007 Aug 15;110(4):1301-7. doi: 10.1182/blood-2006-12-064865. Epub 2007 May 7.
Burkitt lymphoma (BL) is a B-cell tumor whose characteristic gene aberration is the translocation t(8;14), which determines c-myc overexpression. Several genetic and epigenetic alterations other than c-myc overexpression have also been described in BL. It has been demonstrated that the RBL2/p130 gene, a member of the retinoblastoma family (pRbs), is mutated in BL cell lines and primary tumors. The aim of this study was to investigate the biologic effect of RBL2/p130 in BL cells and its possible role in lymphomagenesis. Therefore, we reintroduced a functional RBL2/p130 in BL cell lines where this gene was mutated. Our results demonstrated that RBL2/p130-transfected cells regain growth control. This suggests that RBL2/p130 may control the expression of several genes, which may be important for cell growth and viability. Gene-expression analysis revealed a modulation of several genes, including CGRRF1, RGS1, BTG1, TIA1, and PCDHA2, upon RBL2/p130 reintroduction. We then monitored their expression in primary tumors of endemic BL as well, demonstrating that their expression resembled those of the BL cell lines. In conclusion, these data suggest that, as RBL2/p130 modulates the expression of target genes, which are important for cell growth and viability, its inactivation may be relevant for the occurrence of BL.
伯基特淋巴瘤（BL）是一种B细胞肿瘤，其特征性基因畸变是t(8;14)易位，该易位决定了c-myc的过表达。除了c-myc过表达外，BL中还描述了其他几种遗传和表观遗传改变。已证明视网膜母细胞瘤家族（pRbs）成员RBL2/p130基因在BL细胞系和原发性肿瘤中发生突变。本研究的目的是探讨RBL2/p130在BL细胞中的生物学效应及其在淋巴瘤发生中的可能作用。因此，我们在该基因发生突变的BL细胞系中重新引入了功能性RBL2/p130。我们的结果表明，转染RBL2/p130的细胞恢复了生长控制。这表明RBL2/p130可能控制几个基因的表达，这些基因可能对细胞生长和生存能力很重要。基因表达分析显示，重新引入RBL2/p130后，包括CGRRF1、RGS1、BTG1、TIA1和PCDHA2在内的几个基因发生了调节。然后我们也监测了它们在地方性BL原发性肿瘤中的表达，结果表明它们的表达与BL细胞系的表达相似。总之，这些数据表明，由于RBL2/p130调节对细胞生长和生存能力很重要的靶基因的表达，其失活可能与BL的发生有关。
