title: Monitoring the gene expression profiles of doxorubicin-resistant acute myelocytic leukemia cells by DNA microarray analysis.
abstract: 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.
authors.affiliation: College of Pharmacy and Genome Center for Hematopoietic Diseases, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Ju Han
authors.initials: JH
authors.lastname: Song
authors.forename: Cheol Hee
authors.initials: CH
authors.lastname: Choi
authors.forename: Hye-Jung
authors.initials: HJ
authors.lastname: Yeom
authors.forename: Seung Yong
authors.initials: SY
authors.lastname: Hwang
authors.forename: Tae Sung
authors.initials: TS
authors.lastname: Kim
mesh_terms: 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
chemical_list: D000903:Antibiotics, Antineoplastic; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D004317:Doxorubicin