Target genes downregulated by the BCL-6/LAZ3 oncoprotein in mouse Ba/F3 cells.
The BCL-6/LAZ3 gene encodes a zinc-finger transcriptional repressor and is located at the breakpoint of the 3q27-associated translocations that occur most frequently in non-Hodgkin's lymphomas (NHLs). A number of chromosomal translocations 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 carrying a human BCL-6 transgene that is inducible under control of the lactose operon. Using a cDNA array hybridization technique, we found that the induced BCL-6 protein can downregulate the expressions of the genes, cyclin A2, chemokine receptor CXCR4, and insulin-like growth factor binding protein-4 (IGFBP-4) in the Ba/F3 cells. Northern blot analysis established that the expressions of these genes were indeed downregulated by the induced BCL-6 protein but in a somewhat different manner. The induced BCL-6 protein also inhibited cell proliferation of Ba/F3 cells. These findings strongly suggest that three key genes, namely cyclin A2, CXCR4, and IGFBP-4 may play a role in the downstream of the BCL-6 signaling pathway during B-lymphoid differentiation.
Hosokawa
Y
Y
Division of Molecular Medicine, Aichi Cancer Center Research Institute, 1-1 Kanakoden, Nagoya, Chikusa-ku, 464-8681, Japan. yhosokaw@aichi-cc.pref.aichi.jp
Maeda
Y
Y
Seto
M
M
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D019925:Cyclin A / Q000235:genetics; D056751:Cyclin A2; D004268:DNA-Binding Proteins / Q000235:genetics*; D015536:Down-Regulation; D006801:Humans; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000235:genetics; D007763:Lac Operon; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection
C503721:CCNA2 protein, human; D019925:Cyclin A; D056751:Cyclin A2; D004268:DNA-Binding Proteins; D018974:Insulin-Like Growth Factor Binding Protein 4; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D014157:Transcription Factors