Molecular mechanism of myeloma cell line differentiation induced by 2-methoxyestradiol.
- Author:
Wei-Ran GAO
1
;
Jian HOU
;
Hong XIONG
Author Information
- Publication Type:Journal Article
- MeSH: Cell Differentiation; drug effects; Cell Line, Tumor; DNA-Binding Proteins; genetics; metabolism; Estradiol; pharmacology; Humans; Multiple Myeloma; genetics; metabolism; pathology; RNA, Messenger; genetics; Regulatory Factor X Transcription Factors; Transcription Factors; genetics; metabolism; X-Box Binding Protein 1
- From: Chinese Journal of Hematology 2005;26(10):598-601
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the molecular mechanism of differentiation induction by 2-methoxyestradiol (2ME2) of myeloma cell lines.
METHODSDifferentiation 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.
RESULTS2ME2 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.
CONCLUSION2ME2 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.
