Monitoring the gene expression profiles of doxorubicin-resistant acute myelocytic leukemia cells by DNA microarray analysis.
Acquired drug-resistance phenotype is a key factor in the relapse of patients suffering hematological malignancies. In order to investigate the genes involved in drug resistance, a human leukemia cell line that is resistant to doxorubicin, an anthracycline anticancer agent (AML-2/DX100), was selected and its gene expression profile was analyzed using a cDNA microarray. A number of genes were differentially expressed in the AML-2/DX100 cells, compared with the wild type (AML-2/WT). Pro-apoptotic genes such as TNFSF7 and p21 (Cip1/Waf1) were significantly down-regulated, whereas the IKBKB, PCNA, stathmin 1, MCM5, MMP-2 and MRP1 genes, which are involved in anti-apoptotic or cell cycle progression, were over-expressed. The AML-2/DX100 cells were also resistant to other anticancer drugs, including daunorubicin and camptothecin, and the expression levels of the differentially regulated genes such as STMN1, MMP-2 and CTSG, were constantly maintained. This suggests that the deregulated genes obtained from the DNA microarray analysis in a cell line model of drug resistance might contribute to the acquired drug resistance after chronic exposure.
Song
Ju Han
JH
College of Pharmacy and Genome Center for Hematopoietic Diseases, Chonnam National University, Gwangju, Republic of Korea.
Choi
Cheol Hee
CH
Yeom
Hye-Jung
HJ
Hwang
Seung Yong
SY
Kim
Tae Sung
TS
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004273:DNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics*; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000903:Antibiotics, Antineoplastic; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D004317:Doxorubicin