title: Increased nuclear localization of transcription factor Y-box binding protein 1 accompanied by up-regulation of P-glycoprotein in breast cancer pretreated with paclitaxel.
abstract: OBJECTIVE
  The Y-box binding protein 1 (YB-1) regulates expression of P-glycoprotein encoded by the MDR1 gene. There have been no previous studies regarding the involvement of YB-1 in the development of resistance to paclitaxel. The present study was done to examine how paclitaxel affects the localization and expression of YB-1 in breast cancer.
  
  
  METHODS
  We evaluated the expression and localization of YB-1 and P-glycoprotein in breast cancer tissues obtained from 27 patients before and after treatment with paclitaxel. The effect of paclitaxel on localization of cellular YB-1 was examined by using GFP-YB-1. Interaction of YB-1 with the Y-box motif of the MDR1 promoters was studied by electrophoretic mobility shift assay. The effects of paclitaxel on MDR1 promoter activity were examined by luciferase assay.
  
  
  RESULTS
  Of 27 breast cancer tissues treated with paclitaxel, nine (33%) showed translocation of YB-1 from the cytoplasm to the nucleus together with increased expression of P-glycoprotein during the course of treatment. Twelve breast cancer tissues (44%) showed neither translocation of YB-1 nor increased expression of P-glycoprotein. Nuclear translocation of YB-1 was correlated significantly with increased expression of P-glycoprotein (P=0.0037). Confocal analysis indicated that paclitaxel induced nuclear translocation of green fluorescent fused YB-1 in MCF7 cells. Furthermore, binding of YB-1 to the Y-box of MDR1 promoter was increased in response to treatment with paclitaxel. In addition, MDR1 promoter activity was significantly up-regulated by paclitaxel in MCF7 cells (P<0.001).
  
  
  CONCLUSIONS
  The results of the present study suggested that YB-1 may be involved in the development of resistance to paclitaxel in breast cancer.
authors.affiliation: Department of Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, and Department of Surgery, Niigata Cancer Center Hospital, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Fujita
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Ito
authors.forename: Hiroto
authors.initials: H
authors.lastname: Izumi
authors.forename: Morihiko
authors.initials: M
authors.lastname: Kimura
authors.forename: Muneaki
authors.initials: M
authors.lastname: Sano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakagomi
authors.forename: Kazuma
authors.initials: K
authors.lastname: Maeno
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Hama
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Shingu
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Tsuchiya
authors.forename: Kimitoshi
authors.initials: K
authors.lastname: Kohno
authors.forename: Minoru
authors.initials: M
authors.lastname: Fujimori
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000378:metabolism; D002467:Cell Nucleus / Q000737:chemistry* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use*; D011401:Promoter Regions, Genetic; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D051840:Y-Box-Binding Protein 1 / Q000032:analysis* / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D051840:Y-Box-Binding Protein 1; D017239:Paclitaxel