[Identification of differentially expressed genes involved in multidrug resistance in K562/A02 by cDNA microarray].
OBJECTIVE
To study the molecular mechanism underlying multidrug resistance (MDR) and identify unknown genes that might be involved in drug resistance development in K562/A02 cells.


METHODS
K562/A02 was induced by gradually increasing the ADM concentration in culture medium of K562 cells, the differential expression of associated genes between K562 and K562/A02 was determined with cDNA microarray. Overexpression of neurofilament protein NF-H gene in K562/A02 cells was confirmed with RT-PCR and immunocytochemistry. Anti-sense oligodeoxynucleotides were transfected into K562/A02 cells by lipofectamine in order to further analyze the role of NF-H in drug resistance.


RESULTS
Comparing with the expression profiles, we found upregulation of 5 transcripts and downregulation of 7 transcripts in response to MDR of K562/A02 cells. The overexpression of NF-H, one of the 5 upregulated genes, was confirmed. After being treated with antisense oligodeoxynucleotides of NF-H and mdr1, the cellular adriamycin concentration increased significantly, but antisense NF-H alone did not have significant effect on drug resistance phenotype.


CONCLUSIONS
The development of MDR in K562/A02 cells is multifactorial. NF-H may be involved in the drug resistance of K562/A02, which may provide a new marker of diagnosis and a new target of therapy.
State Key Laboratory of Experimental Hematology, Institute of Hematology, CAMS & PUMC, Tianjin 300020, China.
Yao-hong
YH
Tan
Chun-zheng
CZ
Yang
Chun-hua
CH
Zhao
Jing
J
Qi
Hui
H
Peng
Jian-xiang
JX
Wang
Yuan
Y
Zhou
Ying
Y
Xiao
Lan
L
Lan
D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D019450:Genes, MDR; D006801:Humans; D020014:K562 Cells; D016900:Neurofilament Proteins / Q000096:biosynthesis* / Q000235:genetics; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation
D016900:Neurofilament Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; C051774:neurofilament protein H; D004317:Doxorubicin