The Role Of C-myc Gene In Myeloma Cell Differentiation Induced By 2-methoxyestradiol

Our previous studies showed that 2ME2 at low concentrations could induce differentiation of myeloma cells. Furthermore, we found that the plasmacytic transcription factor Blimp-1, and XBP-1 repressed by Pax-5 were both up-regulated.Proto-oncogene c-myc has been showed to play a pivotal role in the control of proliferation, differentiation and apoptosis. The up-regulation of c-myc expression is one of the pathogenesy of MM. So it is necessary to study the role of c-myc in the differentiation of myeloma cells induced by 2ME2. in this part of our study, exprosed myeloma cell lines to 2-methoxyestradiol at low dose to induce cell differentiation, and cell cycle distribution was analyzed by flow cytometry. The expression of c-myc mRNA and protein was studied by RT-PCR and Western Blot, respectively. In addition, exposure of myeloma cell lines to 2ME2+Blimp-1 ASODN, the expression of c-myc mRNA and the amounts of c-myc protein were observed by RT-PCR and Western Blot. Finally, we constructed pcDNA3. 1-C-MYC plasmid and transfected it into CZ-1 and exposed the pcDNA3.1-C-MYC-CZ-1 cell to 2ME2 to observe the cell line differentiation. The expression of XBP-1 mRNA was studied by RT-PCR. In addition, we also exposed CZ-1 to XBP-1 ASODN and 2ME2, the cell line differentiation was blocked, and the expression of c-myc mRNA was studied by RT-PCR.