Oral carcinogenesis by disturbance of squamous differentiation regulated by Notch1

• Project/Area Number: 25462848
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Sakamoto Kei 東京医科歯科大学, 医歯(薬)学総合研究科, 講師 (00302886)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 口腔癌 / Notch1 / 扁平上皮癌 / ノックアウトマウス / トランスジェニックマウス / 癌 / 上皮異形成 / ケラチン / 上皮性異形成

Outline of Final Research Achievements

We conducted chemical carcinogenesis experiments on mice by administering a carcinogenic agent by drinking water. Cancers and precancerous lesions like those of human developed in the oral cavity and esophagus. Ｗe created epithelial-specific conditional Notch1-knockout mice. These mice exhibited patchy hair loss with hyperplasia of hair follicles. Chemical carcinogenesis experiments revealed increased incidence of esophageal cancer in these mice compared with the wild type littermates. These results indicated that Notch1 plays an important role in development of oroesophageal cancer as a tumor-suppressor gene.

Research Products

• [Journal Article] A facile one-step strategy for the generation of conditional knockout mice to explore the role of Notch1 in oroesophageal tumorigenesis. (2016)
  • Author(s): Mandasari M, Sawangarun W, Katsube K, Kayamori K, Yamaguchi A, Sakamoto K
  • Journal Title: Biochem Biophys Res Commun Volume: 469(3) Issue: 3 Pages: 761-767
  • DOI: 10.1016/j.bbrc.2015.12.006
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Conditional Notch1-knockout Transgenic Mouse Generation by CRISPR/Cas9 Genome Engineering System (2015)
  • Author(s): M Mandasari, W Sawangarun, A Yamaguchi, K Sakamoto
  • Organizer: IADR South East Asia Division Annual Scientific Meeting
  • Place of Presentation: Bali, Indonesia
  • Year and Date: 2015-08-14
  • Int'l Joint Research
• [Presentation] Notch1 expression is downregulated in chemically-induced oral epithelial dysplasia
  • Author(s): マシタ マンダサリ、坂本 啓、山口 朗
  • Organizer: 第24回日本臨床口腔病理学会総会・学術大会
  • Place of Presentation: 東京