HUMAN NON-SMALL CELLLUNG CANCER TARGETED PROMOTER SYSTEM FOR GENE THERAPY

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 18591548
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Okayama University
• Principal Investigator: MATSUOKA Junji Okayama University, Medical and Dental Hospital, Assistant Professor (30332795)
• Co-Investigator(Kenkyū-buntansha): TANAKA Noriaki Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Professor (10127566) ; FUKAZAWA Takuya Okayama University, Medical School, Visiting Researcher (20379845) ; TANAKA Hirotoshi The University of Tokyo, The institute of Medical Science, Associate Professor (00171794)
• Project Period (FY): 2006 – 2007
• Keywords: Lung cancer / Surfactant protein A / Thyroid transcription factor 1 / Glucocorticoid

Research Abstract

Gene therapy is one of the approaches used to treat lung cancer. The benefit of cancer gene therapy is that different types of tumors can be selectively targeted by tumor specific expression of therapeutic genes that include an apoptosis gene to destroy the tumor. Previously, we described a promoter (TTS promoter) that we designed that is specifically targeted to lung cancer cells but not to other types of cancer or normal cells including stem cells. In this pursuit, we further characterized the specificity of the TTS promoter in four types of lung cancer cells (squamous cell lung carcinoma, pulmonary adenocarcinoma, small-cell lung carcinoma, large-cell lung carcinoma). The TTS promoter was highly active only in pulmonary adenocarcinoma cells but not in the other three types of lung cancer cells. The specificity seemed to be derived from transcription factor thyroid transcription factor 1 associating cofactors that affect human surfactant protein Al promoter activity in pulmonary adenocarcinoma. We inserted the proapoptotic gene Bcl-2 associated X protein (Bax) into the TTS promoter (TTS/Bax). The TTS/Bax selectively caused BAX expression and cell death in pulmonary adenocarcinoma but not in other cells. Cell death caused by the BAX expression was also observed in pulmonary adenocarcinoma that is resistant to the promoter, anticancer drug gefitinib (epidermal growth factor receptor tyrosine kinase inhibitor). BAX expression and cell death can be suppressed by dexamethasone (a glucocorticoid) treatment through negative glucocorticoid elements in the TTS promoter.

Research Products

• [Journal Article] Pulmonary adenocarcinoma targeted gene therapy by a cancer-and tissue-specific promoter system (2007)
  • Author(s): Fukazawa T, et. al.
  • Journal Title: Mol Cancer Ther. 6 Pages: 244-252
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Pulmonary adenocarcinoma-targeted gene therapy by a cancer-and tissue-specific promoter system (2007)
  • Author(s): Fukazawa, T., Maeda, Y., Durbin, ML., Nakai, T., Matsuoka, J., Tanaka, H., Naomoto, Y., Tanaka, N
  • Journal Title: Mol Cancer Then 6 Pages: 244-252
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 組織かつ癌特異的目的遺伝子発現システムによる肺腺癌治療への応用 (2006)
  • Author(s): 深澤拓也, 松岡順治 以下8名
  • Organizer: 第65回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 20060900
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] HUMAN NON-SMALL CELL LUNG CANCER TARGETED PROMOTER SYSTEM FOR GENE THERAPY (2006)
  • Author(s): Fukazawa, T., Matsuoka, J., Naomoto, Y., Nakai, T., Maeda, Y., Frances, M., Sladek, Laurie, B., Owen-Schaub, Jeffrey, Whitsett, Tanaka, N
  • Organizer: 65th Annual Meeting of Japanese Association for Cancer Research
  • Place of Presentation: Yokohama
  • Year and Date: 20060900
  • Description: 「研究成果報告書概要(欧文)」より