[Molecular mechanism of myeloma cell line differentiation induced by 2-methoxyestradiol].
OBJECTIVE
To study the molecular mechanism of differentiation induction by 2-methoxyestradiol (2ME2) of myeloma cell lines.


METHODS
Differentiation induction effect on myeloma cell lines LP-1, CZ-1 and NCI-H929 which were incubated with 2ME2 and XBP-1, Blimp-1, pax-5 phosphorothioate antisense oligodeoxynucleotide (ASODN) was evaluated by cell morphology, CD49e expression, quantitation of light chain secretion, and the level of pax-5 and XBP-1 mRNA expression.


RESULTS
2ME2 caused morphological, immunophenotypic and the supernatant light chain secretion changes typical of differentiation in all the three myeloma cell lines. 2ME2 up-regulated the XBP-1 mRNA expression. XBP-1 and Blimp-1 ASODNs partially inhibited the differentiation of LP-1, CZ-1, NCI-H929 cells induced by 2ME2; whereas pax-5 ASODN did the contrary. After incubated with pax-5 ASODN for 72 hours, LP-1, CZ-1, NCI-H929 cells exhibited characteristic morphologic feature of differentiation. The expression of CD49e was increased statistically (P < 0.05). Light chain secretion in the supernatant was also increased statistically (P < 0.05). After incubation with Blimp-1 ASODN, the level of XBP-1 mRNA was declined, while the level of pax-5 mRNA increased.


CONCLUSIONS
2ME2 could induce cell differentiation and up-regulate XBP-1 mRNA expression in myeloma cell lines. Blimp-1 could help 2ME2 with inducing differentiation of myeloma cells through downregulating pax-5 mRNA and upregulating XBP-1 mRNA.
Gao
Wei-Ran
WR
Department of Hematology, Changzheng Hospital, the Second Military Medical University,Shanghai 200003, China.
Hou
Jian
J
Xiong
Hong
H
D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071717:X-Box Binding Protein 1
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; D004958:Estradiol