title: Establishment of new intraperitoneal paclitaxel-resistant gastric cancer cell lines and comprehensive gene expression analysis.
abstract: BACKGROUND
  Intraperitoneal (i.p.) chemotherapy with paclitaxel is a potential therapeutic modality for patients with peritoneal metastasis of gastric cancer. To overcome paclitaxel resistance, which is a major clinical problem with this modality, prediction of i.p. paclitaxel resistance is critically important.
  
  
  METHODS
  We developed three new i.p. paclitaxel-resistant cell lines from parental gastric cancer cell lines by an in vivo selection method using i.p. paclitaxel chemotherapy. With these cell lines, we performed gene expression profiling analysis to select up-regulated genes in i.p. paclitaxel-resistant cells and validated the genes with clinical samples.
  
  
  RESULTS
  We successfully isolated nine up-regulated genes in i.p. paclitaxel-resistant cell lines compared with parental cells by microarray analysis, followed by confirmation with quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Among these, we identified four genes, namely kinesin family member-23 (KIF23), ERBB2 interacting protein (ERBB2IP), ATPase family, AAA domain containing-2 (ATAD2) and PHD finger protein (PHF19) as candidate genes for paclitaxel resistance after validation with clinical samples derived from responders and non-responders to paclitaxel treatment.
  
  
  CONCLUSIONS
  These i.p. paclitaxel-resistant cell lines are ideal models for understanding the mechanism of resistance to i.p. paclitaxel and development of a new therapeutic modality. Four up-regulated genes may be potential new predictive markers for resistance to i.p. paclitaxel in patients with peritoneal metastasis of gastric cancer.
authors.affiliation: Division of Oncological Pathology, Aichi Cancer Center Research Institute, 464-8681, Kanokoden, 1-1, Chikusa-ku, Nagoya 464, Japan. Fax: +81 527635233, hnakanis@aichi-cc.jp.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Murakami
authors.forename: Seiji
authors.initials: S
authors.lastname: Ito
authors.forename: Harunari
authors.initials: H
authors.lastname: Tanaka
authors.forename: Eisaku
authors.initials: E
authors.lastname: Kondo
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kodera
authors.forename: Hayao
authors.initials: H
authors.lastname: Nakanishi
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000368:Aged; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D017239:Paclitaxel / Q000494:pharmacology*; D010529:Peritoneal Cavity / Q000473:pathology; D013274:Stomach Neoplasms / Q000188:drug therapy*; D014157:Transcription Factors; D059467:Transcriptome; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000972:Antineoplastic Agents, Phytogenic; D004268:DNA-Binding Proteins; C413364:ERBIN protein, human; C092935:KIF23 protein, human; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C497703:PHF19 protein, human; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; C544857:ATAD2 protein, human; D000074183:ATPases Associated with Diverse Cellular Activities; D017239:Paclitaxel
keywords: Gastric cancer cell lines; gene expression profile; in vivo selection; paclitaxel-resistance; peritoneal metastasis