Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
2-Methoxyestradiol
-
Blotting, Western
-
Cell Cycle / drug effects
-
Cell Differentiation / drug effects*
-
Cell Line, Tumor
-
Cell Proliferation / drug effects
-
DNA Primers
-
DNA-Binding Proteins / antagonists & inhibitors
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / metabolism*
-
Estradiol / analogs & derivatives*
-
Estradiol / pharmacology
-
Flow Cytometry
-
Humans
-
Multiple Myeloma / pathology*
-
Nuclear Proteins / antagonists & inhibitors
-
Nuclear Proteins / genetics
-
Nuclear Proteins / metabolism*
-
Positive Regulatory Domain I-Binding Factor 1
-
Proto-Oncogene Proteins c-myc / genetics
-
Proto-Oncogene Proteins c-myc / metabolism*
-
RNA, Messenger / genetics
-
RNA, Messenger / metabolism
-
Regulatory Factor X Transcription Factors
-
Repressor Proteins / genetics
-
Repressor Proteins / metabolism
-
Reverse Transcriptase Polymerase Chain Reaction
-
Signal Transduction
-
Transcription Factors / genetics
-
Transcription Factors / metabolism
-
Tubulin Modulators / pharmacology*
-
X-Box Binding Protein 1
Substances
-
DNA Primers
-
DNA-Binding Proteins
-
Nuclear Proteins
-
Proto-Oncogene Proteins c-myc
-
RNA, Messenger
-
Regulatory Factor X Transcription Factors
-
Repressor Proteins
-
Transcription Factors
-
Tubulin Modulators
-
X-Box Binding Protein 1
-
XBP1 protein, human
-
PRDM1 protein, human
-
Estradiol
-
2-Methoxyestradiol
-
Positive Regulatory Domain I-Binding Factor 1