Gene expression analysis identifies novel RBL2/p130 target genes in endemic Burkitt's lymphoma cell lines and primary tumors

Authors:
De Falco G, Leucci E, Lenze D, Piccaluga PP, Claudio PP, Onnis A, Cerino G, Nyagol J, Mwanda W, Bellan C, Hummel M, Pileri S, Tosi P, Stein H, Giordano A, Leoncini L
In:
Source: Blood
Publication Date: (2007)
Issue: 110(4): 1301-7
Research Area:
Cancer Research/Cell Biology
Immunotherapy / Hematology
Cells used in publication:
Daudi
Species: human
Tissue Origin:
Raji
Species: human
Tissue Origin:
Platform:
Nucleofectorâ„¢ I/II/2b
Abstract
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 biological 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.