Target genes downregulated by the BCL-G/LAZ3 oncoprotein in mouse Ba/F3 cells

BCL-6/LAZ3 gene encodes a zinc-finger transcriptional repressor and is loca ted at the breakpoint of the 3q27-associated translocations that occur most frequently in non-Hodgkin's lymphomas (NHLs). A number of chromosomal tran slocations involving BCL-6 have been analyzed, but the biological functions of this protein remain obscure. To examine cell responses and target genes related to the BCL-6 signaling pathway, we established Ba/F3 pro-B cells c arrying a human BCL-6 transgene that is inducible under control of the lact ose operon. Using a cDNA array hybridization technique, we found that the i nduced BCL-6 protein can downregulate the expressions of the genes, cyclin. A2, chemokine receptor CXCR4 and insulin-like growth factor binding protei n-4 (IGFBP-4) in the Ba/F3 cells. Northern blot analysis established that t he expressions of these genes were indeed downregulated by the induced BCL- 6 protein but in a somewhat different manner. The induced BCL-6 protein als o inhibited cell proliferation of Ba/F3 cells. These findings strongly sugg est that three key genes, namely cyclin A2, CXCR4 and IGFBP-4 may play a ro le in the downstream of the BCL-6 signaling pathway during B-lymphoid diffe rentiation. (C) 2001 Academic Press.