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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. 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.

journal_name

Clin Lung Cancer

journal_title

Clinical lung cancer

authors

Hyogotani A,Ito K,Yoshida K,Izumi H,Kohno K,Amano J

doi

10.1016/j.cllc.2011.11.006

subject

Has Abstract

pub_date

2012-09-01 00:00:00

pages

375-84

issue

5

eissn

1525-7304

issn

1938-0690

pii

S1525-7304(11)00294-4

journal_volume

13

pub_type

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