title: Identification of genes with differential expression in acquired drug-resistant gastric cancer cells using high-density oligonucleotide microarrays.
abstract: OBJECTIVE
  A major obstacle in chemotherapy is treatment failure due to anticancer drug resistance. The emergence of acquired resistance results from host factors and genetic or epigenetic changes in the cancer cells. The purpose of this study was to identify differentially expressed genes associated with acquisition of resistance in human gastric cancer cells.
  
  
  METHODS
  We performed global gene expression analysis in the acquired drug-resistant gastric cancer cell lines to the commonly used drugs 5-fluorouracil, doxorubicin, and cisplatin using Affymetrix HG-U133A microarray. The gene expression patterns of 10 chemoresistant gastric cancer cell lines were compared with those of four parent cell lines using fold-change and Wilcoxon's test for data analysis.
  
  
  RESULTS
  We identified over 250 genes differentially expressed in 5-fluorouracil-, cisplatin-, or doxorubicin-resistant gastric cancer cell lines. Our expression analysis also identified eight multidrug resistance candidate genes that were associated with resistance to two or more of the tested chemotherapeutic agents. Among these, midkine (MDK), a heparin-binding growth factor, was overexpressed in all drug-resistant cell lines, strongly suggesting that MDK might contribute to multidrug resistance in gastric cancer cells.
  
  
  CONCLUSIONS
  Our investigation provides comprehensive gene information associated with acquired resistance to anticancer drugs in gastric cancer cells and a basis for additional functional studies.
authors.affiliation: Laboratory of Cell Biology, Cancer Research Institute and Cancer Research Center, Seoul National University, Seoul, Korea.
authors.forename: Hio Chung
authors.initials: HC
authors.lastname: Kang
authors.forename: Il-Jin
authors.initials: IJ
authors.lastname: Kim
authors.forename: Jae-Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Yong
authors.initials: Y
authors.lastname: Shin
authors.forename: Ja-Lok
authors.initials: JL
authors.lastname: Ku
authors.forename: Mi Sun
authors.initials: MS
authors.lastname: Jung
authors.forename: Byong Chul
authors.initials: BC
authors.lastname: Yoo
authors.forename: Hark Kyun
authors.initials: HK
authors.lastname: Kim
authors.forename: Jae-Gahb
authors.initials: JG
authors.lastname: Park
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology; D016207:Cytokines; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D000078792:Midkine; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002352:Carrier Proteins; D016207:Cytokines; D009363:Neoplasm Proteins; D000078792:Midkine; D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil