Nuclear Y-box binding protein-1, a predictive marker of prognosis, is correlated with expression of HER2/ErbB2 and HER3/ErbB3 in non-small cell lung cancer

Masaki Kashihara, Koichi Azuma, Akihiko Kawahara, Yuji Basaki, Satoshi Hattori, Takashi Yanagawa, Yasuhiro Terazaki, Shinzo Takamori, Kazuo Shirouzu, Hisamichi Aizawa, Kenji Nakano, Masayoshi Kage, Michihiko Kuwano, Mayumi Ono

研究成果: ジャーナルへの寄稿学術誌査読

46 被引用数 (Scopus)

抄録

INTRODUCTION: Nuclear expression of Y-box binding protein-1 (YB-1) is closely associated not only with global drug resistance and expression of several growth factor receptors in various human malignancies but also with overall patient survival. METHODS: The effect of YB-1 knockdown on expression of epidermal growth factor receptor (EGFR) family proteins was examined by Western blot using human lung cancer cell lines. Immunohistochemistry was used to evaluate the expression of nuclear YB-1 and EGFR family proteins in patients with non-small cell lung cancer (NSCLC) (n = 104). RESULTS: In the five NSCLC cell lines, expressions of EGFR, human epidermal growth factor receptor 2 (HER2), HER3, and hepatocyte growth factor receptor (c-Met) in PC-9 cells; of HER2 and c-Met in EBC-1 cells; and of HER3 in QG56 cells were down-regulated by YB-1 knockdown. By immunohistochemical analysis, we observed that HER3 expression was significantly negatively correlated with nuclear YB-1 expression in squamous cell carcinoma (p = 0.038). HER2 expression was positively correlated with nuclear YB-1 expression in adenocarcinoma (p = 0.052). Nuclear expression of YB-1 correlated with overall survival of all patients (p = 0.028) and of patients with adenocarcinoma (p = 0.007). Furthermore, there was a significant difference in therapeutic efficacies of gefitinib between patients with nuclear YB-1 expression and those with non-nuclear YB-1 expression in patients with NSCLC (p = 0.004, n = 26) but not between those with high and those with low expression of EGFR, HER2, HER3, and c-Met. CONCLUSION: Nuclear YB-1 expression might be essential for the malignant phenotype in lung cancer patients and might be an important biomarker for the development of therapeutic strategy against NSCLC.

本文言語英語
ページ(範囲)1066-1074
ページ数9
ジャーナルJournal of Thoracic Oncology
4
9
DOI
出版ステータス出版済み - 9月 2009
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 呼吸器内科

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