title: ERas enhances resistance to CPT-11 in gastric cancer.
abstract: OBJECTIVE
  We have reported that embryonic stem cell-expressed Ras (ERas) is expressed in human gastric cancer and is associated with its tumorigenicity. Here, we asked whether ERas plays a role in resistance to chemotherapy in gastric cancer.
  
  
  METHODS
  To assess the cytotoxicity of chemotherapeutic agents, ERas-overexpressing human gastric cancer GCIY cells were exposed to anticancer agents, including CPT-11 and inhibitor of mammalian target of rapamycin (mTOR). We also investigated the mechanisms by which ERas induces chemoresistance.
  
  
  RESULTS
  ERas-overexpressing clones were significantly more resistant to CPT-11 than were the control (p<0.001). Administration of rapamycin was significantly cytotoxic to the ERas-overexpressing clones compared with the control (p<0.01). Electrophoresis mobility shift assay revealed that ERas enhanced nuclear factor (NF)-κB activity. PCR array demonstrated that ERas up-regulated several multidrug efflux transporter genes, including ABCG2.
  
  
  CONCLUSIONS
  ERas induces chemoresistance to CPT-11 via activation of phosphatidylinositol-3 kinase-protein kinase β mTOR pathway and NF-κB, and consequently results in up-regulation of ABCG2.
authors.affiliation: Department of Gastroenterology and Metabolism, Nagoya City University, Graduate School of Medical Sciences. 1 Kawasumi, Mizuho, Nagoya 467-8601, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kubota
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kataoka
authors.forename: Mamoru
authors.initials: M
authors.lastname: Tanaka
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Masahide
authors.initials: M
authors.lastname: Ebi
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Hirata
authors.forename: Kenji
authors.initials: K
authors.lastname: Murakami
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Mizoshita
authors.forename: Takaya
authors.initials: T
authors.lastname: Shimura
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Mori
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanida
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kamiya
authors.forename: Mineyoshi
authors.initials: M
authors.lastname: Aoyama
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Asai
authors.forename: Takashi
authors.initials: T
authors.lastname: Joh
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D000077146:Irinotecan; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D000077146:Irinotecan; D004247:DNA; D018631:ras Proteins; D004264:DNA Topoisomerases, Type I; D020123:Sirolimus; D002166:Camptothecin