Investigation of Imprinting mechanism between Beckwith-Wiedemann syndrome and Wilms tumor

2012 Fiscal Year Final Research Report

• Project/Area Number: 22591986
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatric surgery
• Research Institution: Nihon University
• Principal Investigator: KOSHINAGA Tsugumiti 日本大学, 医学部, 教授 (70205376)
• Co-Investigator(Kenkyū-buntansha): SUGITO Kiminobu 日本大学, 医学部, 助教 (10328750) ; OOHASHI Kensuke 日本大学, 医学部, 助手 (10526065) ; FURUYA Takeshi 日本大学, 医学部, その他 (20568539) ; FUJIWARA Kyouko 日本大学, 医学部, 助教 (40595708)
• Project Period (FY): 2010 – 2012
• Keywords: Imprinting 異常 / PI ポリアミド / 小児外科

Research Abstract

In Beckwith Wiedeman syndrome(BWS), which occur in conjunction with Wilms tumor at high rates, DNA demethylation of KvDMR domain on chromosome 11p15.5 has been frequently observed. In fact, absolute or relative overexpression of KCNQ1OT1 gene inhibits circumjacent genes on same allele. To suppress KCNQ1OT1 gene expression, two PI polyamides were designed to recognize CCAAT box of promoter region. After the treatment with those PI polyamides, significant down-regulation of KCNQ1OT1 gene and growth inhibition were observed in G401(Wilms tumor cell lines). The results indicate that these PI polyamides could be new therapeutic agents for Wilms tumor and other tumors which has Loss of Imprinting in KvDMR domain.

Research Products

• [Presentation] LIT1遺伝子を標的としたPYRROLE-IMIDAZOLE POLYAMIDE(PIP)の抗腫瘍効果の検討 (2013)
  • Author(s): 吉澤信輔,杉藤公信,星玲奈,植草省太,川島弘之,古屋武史,金田英秀,細田利史,大橋研介,池田太郎,越永従道,藤原恭子,相馬正義,永瀬浩喜.
  • Organizer: 第113回日本外科学会総会
  • Place of Presentation: 福岡
  • Year and Date: 20130500
• [Presentation] Inhibition of LIT1 Gene Transcriptionby Pyrrole-Imidazole Polyamide in Beckwith-Wiedemann syndrome fibroblast cell lines (2012)
  • Author(s): Shinsuke Yoshizawa, Kiminobu Sugito, ShotaUekusa, Hiroyuki Kawashima, ReinaHoshi, Takeshi Furuya, Hide Kaneda, Toshifumi Hosoda, Takayuki Masuko, Taro Ikeda, Tsugumichi Koshinaga, Kyoko Fujiwara, Hiroki Nagase.
  • Organizer: 44th International Society of Paediatric Oncology.
  • Place of Presentation: London,England
  • Year and Date: 20121000
• [Presentation] Inhibition of LIT1 Gene Transcriptionby PI Polyamide(PIP) in Beckwith-Wiedemann syndrome(BWS) fibroblast cell lines (2012)
  • Author(s): Shinsuke Yoshizawa, Shota Uekusa, Hiroyuki Kawashima, Kyoko Fujiwara,HirokiNagase
  • Organizer: 第71回日本癌学会総会
  • Place of Presentation: 札幌
  • Year and Date: 20121000
• [Presentation] Beckwith-Wiedemann症候群細胞株におけるPyrrole-Imidazole Polyamide(P-IPolyamide)によるp57^<KIP2>遺伝子の発現調節 (2012)
  • Author(s): 吉澤信輔,杉藤公信,星玲奈,植草省太,大橋研介,池田太郎,越永従道,藤原恭子,相馬正義
  • Organizer: 第49回日本小児外科学会総会
  • Place of Presentation: 横浜
  • Year and Date: 20120500
• [Presentation] PIポリアミドによる腫瘍抑制遺伝子p57KIP2の再発現の検討 (2012)
  • Author(s): 吉澤信輔,杉藤公信,星玲奈,植草省太,大橋研介,井上幹也,池田太郎,越永従道,相馬正義,麦島秀雄.
  • Organizer: 第112回日本外科学会総会
  • Place of Presentation: 幕張
  • Year and Date: 20120400
• [Presentation] Beckwith-Wiedemann症候群細胞株におけるPyrrole-Imidazole Polyamide(P-I Polyamide)によるp57KIP2遺伝子の発現調節 (2011)
  • Author(s): 吉澤信輔,杉藤公信,星玲奈,植草省太,大橋研介,池田太郎,越永従道,藤原恭子,相馬正義.
  • Organizer: 第53回日本小児血液・がん学会学術集会
  • Place of Presentation: 前橋
  • Year and Date: 20111100