[Changes of gene expression profile in homoharringtonine-induced leukemia multi-drug resistant cell line K562/HHT].

Abstract

OBJECTIVE:

To study the resistant related molecules of human leukemia drug resistant K562 cells (K562/HHT) induced by homoharringtonine (HHT).

METHODS:

Gene expression profiles on K562/HHT, K562 and K562/HHT/RU486 (K562/HHT reversed by RU486) cells were detected by DNA microarray. The bone marrow tyrosine kinase gene in chromosome X (BMX) which changed dynamically among the three cells was confirmed by RT-PCR and Western blot. Then, BMX was transfected into K562 and K562/HHT cells, and the changes of daunorubicin (DNR) concentrations in these two cells were observed for BMX overexpression.

RESULTS:

As compared with K562, there were changes in 117 gene expressions in K562/HHT, 57 of which were up-regulated and 60 down-regulated. The mdrl gene was significantly up-regulated. When compared with K562/HHT, 50 significantly differently expressed genes were screened out in the K562/HHT/RU486 cells, of which up- and down-regulated genes were 13 and 37 respectively. These genes involved in drug resistance, cell signaling, cell differentiation, cell proliferation, transcription regulator, ion transport and so on. Four genes [NM-001721 (BMX), NM-031459 (SESN2), NM-033642 (FGF13) and AL-049309 (SFRS12)] expressed significantly differently in the two group cells, BMX gene expression was higher in K562/HHT, than in K562, but lower than in K562/HHT/RU486 as confirmed by RT-PCR and Western blot. After the plasmid pCI-neo-BMX was transfected into K562 and K562/HHT cells, DNR concentration was significantly lower (79.28 +/- 4.04, 29.84 +/- 2.67) than those before transfection (158.52 +/- 8.08, 58.58 +/- 6.53).

CONCLUSION:

BMX is associated with multi-drug resistance of K562/HHT cell line.

• Authors: Xiao-Lin Yu, Yong Liu, Juan-Dong Wang, De-Xiao Kong, Chun-Yan Chen
• Journal: Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi (Zhonghua Xue Ye Xue Za Zhi) Vol. 30 Issue 6 Pg. 363-7 (Jun 2009) ISSN: 0253-2727 [Print] China
• PMID: 19951526 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Harringtonines
• Homoharringtonine
• BMX protein, human
• Protein-Tyrosine Kinases

Topics

• Drug Resistance, Multiple (drug effects, genetics)
• Drug Resistance, Neoplasm (drug effects, genetics)
• Gene Expression Profiling
• Harringtonines (pharmacology)
• Homoharringtonine
• Humans
• K562 Cells
• Leukemia (drug therapy, genetics, metabolism)
• Protein-Tyrosine Kinases (genetics, metabolism)