Chemosensitivity and microRNA signature in esophageal cancer

• Project/Area Number: 15K10084
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Tohoku University
• Principal Investigator: Saiki Yuriko 東北大学, 医学系研究科, 助教 (80311223)
• Co-Investigator(Kenkyū-buntansha): 小川 武則 東北大学, 大学病院, 講師 (50375060)
• Co-Investigator(Renkei-kenkyūsha): Takeuchi Hiroya 慶應義塾大学, 医学部, 准教授 (20265838)
• Research Collaborator: Sunamura Makoto 東北大学, 医学系研究科, 講師 (10201584)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: esophageal cancer / microRNA / chemosensitivity / ABCB1 / esophagel cancer / head and neck cancer / タキサン耐性 / エピジェネティクス / マイクロRNA

Outline of Final Research Achievements

We established taxane resistant esophageal cancer cell lines and explored possible mechanisms for the acquisition of chemoresistance. We found that the ABCB1 gene encoding a member of the ATP binding cassette (ABC) transporter proteins was significantly upregulated in taxane resistant esophageal cancer cell lines. Moreover, ABCB1 amplification was found in taxane resistant cells. In addition, after treatment with 5-Aza and/or TSA in parental TE1 cell line, ABCB1 was upregulated; epigenetic mechanism may be involved. Analyses of CpG islands within the downstream promoter demonstrated that taxane resistant cells showed unmethylated CGI whereas parental cells were dominantly methylated. In conclusion, ABCB1 gene amplification alongside with alteration in epigenetic mechanism could be responsible for acquisition of taxane resistance in esophageal cancer cells.

Research Products

• [Journal Article] Surgical technique for allogeneic uterus transplantation in macaques (2016)
  • Author(s): Obara H, Kisu I, Kato Y, Yamada Y, Matsubara K, Emoto K, Adachi M, Matoba Y, Umene K, Nogami Y, Banno K, Tsuchiya H, Itagaki I, Kawamoto I, Nakagawa T, Ishigak Hi, Itoh Y, Ogasawara K, Saiki Y, Sato S-i, Nakagawa N, Shiina T, Aoki D, Kitagawa Y
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 35989-35989
  • DOI: 10.1038/srep35989
  • Peer Reviewed / Open Access
• [Presentation] ABCB1 in side populations is a key ABC transporter essential for acquired taxane-chemoresistance in esophageal cancer cells (2015)
  • Author(s): 齋木由利子
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際展示場（名古屋市）
  • Year and Date: 2015-10-08