Synchronous Alterations of Wnt and EGFR Signaling Pathways Through Aberrant Methylation and Mutation in Non-small Cell Lung Cancer

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  • Suzuki Makoto
    Department of Thoracic Surgery, Graduate School of Medicine, Chiba University
  • Shigematsu Hisayuki
    Department of Chest Surgery, NHO Okayama Medical Center
  • Nakajima Takahiro
    Department of Thoracic Surgery, Graduate School of Medicine, Chiba University
  • Motohashi Shinichiro
    Department of Thoracic Surgery, Graduate School of Medicine, Chiba University
  • Sekine Yasuo
    Department of Thoracic Surgery, Graduate School of Medicine, Chiba University
  • Shibuya Kiyoshi
    Department of Thoracic Surgery, Graduate School of Medicine, Chiba University
  • Iizasa Toshihiko
    Department of Thoracic Surgery, Graduate School of Medicine, Chiba University
  • Hiroshima Kenzo
    Department of Basic Pathology, Graduate School of Medicine, Chiba University
  • Nakatani Yukio
    Department of Basic Pathology, Graduate School of Medicine, Chiba University
  • Fujisawa Takehiko
    Department of Thoracic Surgery, Graduate School of Medicine, Chiba University
  • Yoshino Ichiro
    Department of Thoracic Surgery, Graduate School of Medicine, Chiba University

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Other Title
  • 原発性非小細胞肺癌におけるＷｎｔシグナルとＥＧＦＲシグナルの同期的異常

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Description

Objective. The Wnt and EGFR signaling pathways play crucial roles in the pathogenesis of a variety of malignant tumors. While the details of each cascade are understood, very little is known about their collective effects in non-small cell lung cancer (NSCLC). Methods. A total of 238 NSCLC samples were examined for methylation of Wnt antagonists (sFRP-1, sFRP-2, sFRP-5, Wif-1, Dkk-3) and for EGFR and KRAS mutations. Protein expression levels of β-catenin were assayed in 91 of the 238 NSCLCs. Results. We found that (a) aberrant methylation of Wnt antagonists is common in NSCLCs; (b) methylation of sFRP-2 is more prevalent in females, non-smokers, and adenocarcinoma cases; (c) there is a positive correlation between activated EGFR mutation and nuclear accumulation of β-catenin; (d) KRAS mutation and aberrant methylation of Wnt antagonists are positively correlated; and (e) EGFR mutation is significantly associated with a good prognosis in tumors lacking methylated Wnt antagonist genes. Conclusion. These results contribute to a better understanding of the cross-talk between the Wnt and EGFR signaling pathways, and help foster development of chemotherapeutic treatments in NSCLCs.<br>

Journal

  • Haigan

    Haigan 49 (4), 416-421, 2009

    The Japan Lung Cancer Society

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