Coordination of upregulated XBP-1 and downregulated c-myc during myeloma cell differentiation induced by 2-methoxyestradiol.

Our previous studies showed that 2-methoxyestradiol (2ME2) at low concentrations (0.1-0.5 micromol/l) could induce differentiation of myeloma cells, and transcription factors Blimp-1 and XBP-1 repressed by Pax-5 were both upregulated. The present study was aimed at elucidating the molecular mechanism underlying 2ME2-induced myeloma cell differentiation. We demonstrated that cell differentiation required not only Blimp-1 to upregulate XBP-1expression but also Blimp-1 to inhibit c-myc activity. These two signal transduction pathways worked dependently of each other and synergistically to promote the differentiation process of myeloma cells.