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.
Zhou
Xia
X
Department of Hematology, Changzheng Hospital, The Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
Jiang
Hua
H
Hou
Jian
J
D000077584:2-Methoxyestradiol; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D009101:Multiple Myeloma / Q000473:pathology*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology*; D000071717:X-Box Binding Protein 1
D017931:DNA Primers; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D000071701:Regulatory Factor X Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D050257:Tubulin Modulators; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C087042:PRDM1 protein, human; D004958:Estradiol; D000077584:2-Methoxyestradiol; D000074462:Positive Regulatory Domain I-Binding Factor 1