title: Enhanced expression of nuclear factor I/B in oxaliplatin-resistant human cancer cell lines.
abstract: Oxaliplatin is a third-generation platinum drug that has favorable activity in cisplatin-resistant cells. However, the molecular mechanisms underlying oxaliplatin resistance are not well understood. To investigate the molecular mechanisms involved, resistant cell lines were independently derived from colon cancer (DLD1) and bladder cancer (T24) cells. Oxaliplatin-resistant DLD1 OX1 and DLD1 OX2 cell lines were approximately 16.3-fold and 17.8-fold more resistant to oxaliplatin than the parent cell lines, respectively, and had 1.7- and 2.2-fold higher cross-resistance to cisplatin, respectively. Oxaliplatin-resistant T24 OX2 and T24 OX3 cell lines were approximately 5.0-fold more resistant to oxaliplatin than the parent cell line and had 1.9-fold higher cross-resistance to cisplatin. One hundred and fifty-eight genes commonly upregulated in both DLD1 OX1 and DLD1 OX2 were identified by microarray analysis. These genes were mainly involved in the function of transcriptional regulators (14.6%), metabolic molecules (14.6%), and transporters (9.5%). Of these, nuclear factor I/B (NFIB) was upregulated in all oxaliplatin-resistant cells. Downregulation of NFIB rendered cells sensitive to oxaliplatin, but not to cisplatin. Forced expression of NFIB induced resistance to oxaliplatin, but not to cisplatin. Taken together, these results suggest that NFIB is a novel and specific biomarker for oxaliplatin resistance in human cancers.
authors.affiliation: Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kashiwagi
authors.forename: Hiroto
authors.initials: H
authors.lastname: Izumi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yasuniwa
authors.forename: Ryoko
authors.initials: R
authors.lastname: Baba
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Doi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kidani
authors.forename: Tokuzo
authors.initials: T
authors.lastname: Arao
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
authors.forename: Kimitoshi
authors.initials: K
authors.lastname: Kohno
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D051839:NFI Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D051839:NFI Transcription Factors; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin