title: Association of nuclear YB-1 localization with lung resistance-related protein and epidermal growth factor receptor expression in lung cancer.
abstract: BACKGROUND
  Y-box binding protein 1 (YB-1) is an oncogenic transcription factor that is activated in response to various genotoxic stresses. The purpose of this study was to elucidate whether YB-1 correlates with the expression of lung resistance-related protein (LRP) and epidermal growth factor receptor (EGFR) in primary lung cancer.
  
  
  METHODS
  One hundred and five non-small-cell lung cancer (NSCLC) specimens were analyzed by immunohistochemistry. Knockdown of YB-1 messenger RNA by small interfering RNA(siRNA) was tested for the lung cancer cell lines A549 and Calu-3.
  
  
  RESULTS
  Nuclear YB-1 expression significantly correlated with positive LRP and EGFR expression (P < .001). Nuclear YB-1 expression and positive LRP and EGFR expression were independent adverse prognostic factors in patients with NSCLC. Furthermore, patients with tumors positive for nuclear YB-1 and LRP had a significantly worse prognosis than those negative for nuclear YB-1 and LRP (P < .001). In addition, patients with tumors positive for nuclear YB-1 and EGFR had a significantly worse prognosis than those negative for nuclear YB-1 and EGFR (P < .001). In in vitro analyses that use the NSCLC cell lines A549 and Calu-3, the downregulation of YB-1 with siRNAs drastically decreased the expression of EGFR. However, downregulation of YB-1 remarkably decreased the expression of LRP in A549 cells; however, a slight decrease in LRP was induced by the downregulation of YB-1 in Calu-3 cells.
  
  
  CONCLUSIONS
  Our data demonstrate that nuclear YB-1 localization is associated with LRP and EGFR expression in NSCLC, and nuclear YB-1 localization and LRP and EGFR expression are of prognostic significance in NSCLC.
authors.affiliation: Department of Surgery II, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Hyogotani
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Ito
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yoshida
authors.forename: Hiroto
authors.initials: H
authors.lastname: Izumi
authors.forename: Kimitoshi
authors.initials: K
authors.lastname: Kohno
authors.forename: Jun
authors.initials: J
authors.lastname: Amano
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018287:Carcinoma, Large Cell / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality; D002467:Cell Nucleus / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D020394:Vault Ribonucleoprotein Particles / Q000378:metabolism*; D051840:Y-Box-Binding Protein 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000099187:Major Vault Protein
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D034741:RNA, Small Interfering; D020394:Vault Ribonucleoprotein Particles; D051840:Y-Box-Binding Protein 1; D000099187:Major Vault Protein; C070856:YBX1 protein, human; C512478:EGFR protein, human