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 NF-κB 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 (RELΔTAD1) increases the oncogenic properties of the human B-cell lymphoma BJAB cell line, as demonstrated by increased colony formation in soft agar, tumor formation in SCID mice, and adhesion. BJAB-RELΔTAD1 cells also show decreased activation of caspase in response to doxorubicin. BJAB-RELΔTAD1 cells have increased levels of active nuclear REL protein as determined by immunofluorescence, subcellular fractionation, and electrophoretic mobility shift assay. Overexpression of RELΔTAD1 in BJAB cells has transformed the gene expression profile of BJAB cells from that of a germinal center B-cell subtype of diffuse large B-cell lymphoma (GCB-DLBCL) to that of an activated B-cell subtype (ABC-DLBCL), as evidenced by increased expression of many ABC-defining mRNAs. Up-regulated genes in BJAB-RELΔTAD1 cells include several NF-κB 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.