Roles of growth factors and oncogenes on cervical carcinogenesis in transgenic mice

• Project/Area Number: 26462528
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Ehime University
• Principal Investigator: Takashi Matsumoto 愛媛大学, 医学系研究科, 講師 (20346670)
• Co-Investigator(Kenkyū-buntansha): 小泉 雅江 愛媛大学, 医学系研究科, 助教 (60583028) ; 那波 明宏 名古屋大学, 医学系研究科, 特任教授 (90242859)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 腫瘍発生学 / 子宮頸癌 / 動物モデル / トランスジェニックマウス

Outline of Final Research Achievements

In this study, we examined the impact of elevated several growth factors/oncogenes in cervical epithelium of transgenic mice. We generated transgenic mice those overexpressed transforming growth factor-a (TGF-α), c-src or insulin-like growth factor-1 (IGF-1) in epithelial basal cells driven by the keratin 14 (K14) or keratin 5 (K5) promoter. Histopathologic changes were assessed in uterine cervix of 12-month-old TGF-α transgenic mice, Src transgenic mice and IGF-1 transgenic mice, compared to age-matched non-transgenic littermates. The incidence of cervical intraepithelial neoplasia 3 (CIN3) was 37.5% (6/16), 30% (6/20) and 20.8% (5/24) in TGF-α transgenic mice, src transgenic mice and IGF-1 transgenic mice, respectively. Constitutive expression of growth factors/oncogenes, including TGF-α, c-src and IGF-1, and activation of the epidermal growth factor receptor in epithelium of uterine cervix may play an important role in tumorigenesis in this tissue.

Research Products

• [Journal Article] Clinical investigation of the safety and efficacy of a cervical intraepithelial neoplasia treatment using a hyperthermia device that uses heat induced by alternating magnetic fields. (2016)
  • Author(s): Koji Koizumi, Toru Fujioka, Toshiaki Yasuoka, Aya Inoue, Yuka Uchikura, Hiroki Tanaka, Katsuko Takagi, Miki Mori, Masae Koizumi, Hisashi Hashimoto, Takashi Matsumoto, Yuko Matsubara, Keiichi Matsubara, Akihiro Nawa
  • Journal Title: Molecular and Clinical Oncology Volume: 13 Issue: 2 Pages: 310-316
  • DOI: 10.3892/mco.2016.929
  • Peer Reviewed
• [Journal Article] What is an appropriate second-line regimen for recurrent endometrial cancer? Ancillary analysis of the SGSG012/GOTIC004/Intergroup study. (2015)
  • Author(s): Shoji Nagao, Shin Nishio,Satoshi Okada, Takeo Otsuki, Kiyoshi Fujiwara, Hiroshi Tanabe, Masashi Takano, Yoko Hasumi, Yuji Takei, Tetsuya Hasegawa, Takashi Matsumoto, Keiichi Fujiwara, Munetaka Takekuma, Kazuto Nakamura, Muneaki Shimada, Mitsuaki Suzuki, Junzo Kigawa
  • Journal Title: Cancer Chemotherapy Pharmacology Volume: 76 Issue: 2 Pages: 335-342
  • DOI: 10.1007/s00280-015-2793-9
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Surgical Principles for Managing Stage IB2, IIA2, and IIB Uterine Cervical Cancer (Bulky Tumors) in Japan A Survey of the Japanese Gynecologic Oncology Group (2014)
  • Author(s): Mikio Mikami, Yoichi Aoki, Masaru Sakamoto, Muneaki Shimada, Nobuhiro Takeshima, Hisaya Fujiwara, Takashi Matsumoto, Tunekazu Kita, Ken Takizawa
  • Journal Title: International Journal of Gynecological Cancer Volume: 24 Issue: 7 Pages: 1333-1340
  • DOI: 10.1097/igc.0000000000000202
  • Peer Reviewed / Open Access
• [Book] 誰も教えてくれなかった婦人科がん薬物療法 編集：勝俣範之 (2015)
  • Author(s): 松元 隆
  • Total Pages: 159
  • Publisher: メディカルビュー社