BHLHE41/DEC2 Expression Induces Autophagic Cell Death in Lung Cancer Cells and Is Associated with Favorable Prognosis for Patients with Lung Adenocarcinoma

DOI Web Site PubMed 被引用文献1件 参考文献47件 オープンアクセス
  • Toshiyuki Nagata
    Department of General Thoracic Surgery, Graduate School Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan
  • Kentaro Minami
    Department of Molecular Oncology, Graduate School Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan
  • Masatatsu Yamamoto
    Department of Molecular Oncology, Graduate School Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan
  • Tsubasa Hiraki
    Department of Pathology, Graduate School Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan
  • Masashi Idogawa
    Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo 060-8556, Japan
  • Katsumi Fujimoto
    Department of Dental and Medical Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan
  • Shun Kageyama
    Department of Physiology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan
  • Kazuhiro Tabata
    Department of Pathology, Graduate School Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan
  • Kohichi Kawahara
    Department of Molecular Oncology, Graduate School Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan
  • Kazuhiro Ueda
    Department of General Thoracic Surgery, Graduate School Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan
  • Ryuji Ikeda
    Department of Pharmacy, University of Miyazaki Hospital, 5200 Kihara Kiyotake cho, Miyazaki 889-1692, Japan
  • Yukio Kato
    Department of Dental and Medical Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan
  • Masaaki Komatsu
    Department of Physiology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan
  • Akihide Tanimoto
    Department of Pathology, Graduate School Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan
  • Tatsuhiko Furukawa
    Department of Molecular Oncology, Graduate School Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan
  • Masami Sato
    Department of General Thoracic Surgery, Graduate School Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan

説明

<jats:p>Lung cancer constitutes a threat to human health. BHLHE41 plays important roles in circadian rhythm and cell differentiation as a negative regulatory transcription factor. This study investigates the role of BHLHE41 in lung cancer progression. We analyzed BHLHE41 function via in silico and immunohistochemical studies of 177 surgically resected non-small cell lung cancer (NSCLC) samples and 18 early lung squamous cell carcinoma (LUSC) cases. We also examined doxycycline (DOX)-inducible BHLHE41-expressing A549 and H2030 adenocarcinoma cells. BHLHE41 expression was higher in normal lung than in lung adenocarcinoma (LUAD) tissues and was associated with better prognosis for the overall survival (OS) of patients. In total, 15 of 132 LUAD tissues expressed BHLHE41 in normal lung epithelial cells. Staining was mainly observed in adenocarcinoma in situ and the lepidic growth part of invasive cancer tissue. BHLHE41 expression constituted a favorable prognostic factor for OS (p = 0.049) and cause-specific survival (p = 0.042) in patients with LUAD. During early LUSC, 7 of 18 cases expressed BHLHE41, and this expression was inversely correlated with the depth of invasion. DOX suppressed cell proliferation and increased the autophagy protein LC3, while chloroquine enhanced LC3 accumulation and suppressed cell death. In a xenograft model, DOX suppressed tumor growth. Our results indicate that BHLHE41 expression prevents early lung tumor malignant progression by inducing autophagic cell death in NSCLC.</jats:p>

収録刊行物

被引用文献 (1)*注記

もっと見る

参考文献 (47)*注記

もっと見る

関連プロジェクト

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ