Overexpression of an activated REL mutant enhances the transformed state of the human B-lymphoma BJAB cell line and alters its gene expression profile

The human REL proto-oncogene encodes a transcription factor in the nuclear factor (NF)-kappa B family. Overexpression of REL is acutely transforming in chicken lymphoid cells, but has not been shown to transform any mammalian lymphoid cell type. In this report, we show that overexpression of a highly transforming mutant of REL (REL Delta TAD1) increases the oncogenic properties of the human B-cell lymphoma BJAB cell line, as shown by increased colony formation in soft agar, tumor formation in SCID (severe combined immunodeficient) mice, and adhesion. BJAB-RELDTAD1 cells also show decreased activation of caspase in response to doxorubicin. BJAB-REL Delta TAD1 cells have increased levels of active nuclear REL protein as determined by immunofluorescence, subcellular fractionation and electrophoretic mobility shift assay. Overexpression of RELDTAD1 in BJAB cells has transformed the gene expression pro. le of BJAB cells from that of a germinal center B-cell subtype of diffuse large B-cell lymphoma (DLBCL) (GCB-DLBCL) to that of an activated B-cell subtype (ABC-DLBCL), as evidenced by increased expression of many ABC-defining mRNAs. Upregulated genes in BJAB-RELDTAD1 cells include several NF-kappa B targets that encode proteins previously implicated in B-cell development or oncogenesis, including BCL2, IRF4, CD40 and VCAM1. The cell system we describe here may be valuable for further characterizing the molecular details of REL-induced lymphoma in humans. Oncogene (2009) 28, 2100-2111; doi:10.1038/onc.2009.74; published online 20 April 2009