Association of nuclear YB-1 localization with lung resistance-related protein and epidermal growth factor receptor expression in lung cancer

Clin Lung Cancer. 2012 Sep;13(5):375-84. doi: 10.1016/j.cllc.2011.11.006. Epub 2012 Jan 27.

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.

Patients and 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.

Conclusion: 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.

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Large Cell / diagnosis
  • Carcinoma, Large Cell / metabolism
  • Carcinoma, Large Cell / mortality
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / mortality
  • Cell Nucleus / metabolism*
  • ErbB Receptors / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunoenzyme Techniques
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • RNA, Small Interfering / genetics
  • Survival Rate
  • Tumor Cells, Cultured
  • Vault Ribonucleoprotein Particles / metabolism*
  • Y-Box-Binding Protein 1 / antagonists & inhibitors
  • Y-Box-Binding Protein 1 / genetics
  • Y-Box-Binding Protein 1 / metabolism*

Substances

  • Biomarkers, Tumor
  • RNA, Small Interfering
  • Vault Ribonucleoprotein Particles
  • Y-Box-Binding Protein 1
  • YBX1 protein, human
  • major vault protein
  • EGFR protein, human
  • ErbB Receptors