title: Increased expression of metallothionein is associated with irinotecan resistance in gastric cancer.
abstract: To gain insight into clinically relevant mechanisms of irinotecan resistance, we undertook oligonucleotide microarray analyses on paired malignant effusion samples obtained from eight gastric cancer patients treated with weekly irinotecan. Pretreatment and posttreatment (48 h) effusion samples were obtained for each patient, and the change in expression profile was compared between clinical responders and nonresponders. When differences in the expression of genes were examined using SAM (Significance Analysis of Microarrays) software, five isoforms of the metallothionein family were identified to have significantly higher signal log ratios in five nonresponders, compared with three responders. Compared with control cells, metallothionein 1X (MT1X)-transfected AGS cells showed a 1.4-fold higher irinotecan IC(50) by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and tended to form more colonies. These findings collectively suggest that irinotecan-induced up-regulation of metallothionein might be associated with irinotecan resistance in patients with gastric cancer, although it remains to be confirmed in a larger data set.
authors.affiliation: Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Korea.
authors.forename: Jong Ho
authors.initials: JH
authors.lastname: Chun
authors.forename: Hark Kyun
authors.initials: HK
authors.lastname: Kim
authors.forename: Eugene
authors.initials: E
authors.lastname: Kim
authors.forename: In-Hoo
authors.initials: IH
authors.lastname: Kim
authors.forename: Ju Han
authors.initials: JH
authors.lastname: Kim
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Chang
authors.forename: Il Ju
authors.initials: IJ
authors.lastname: Choi
authors.forename: Hyeong-Seok
authors.initials: HS
authors.lastname: Lim
authors.forename: Il-Jin
authors.initials: IJ
authors.lastname: Kim
authors.forename: Hio Chung
authors.initials: HC
authors.lastname: Kang
authors.forename: Jae-Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Jae-Moon
authors.initials: JM
authors.lastname: Bae
authors.forename: Jae-Gahb
authors.initials: JG
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C581554:metallothionein1X, human; D000077146:Irinotecan; D008668:Metallothionein; D002166:Camptothecin