Ink4a/arf-dependent loss of parietal cells induced by oxidative stress promotes CD44-dependent gastric tumorigenesis

Ryo Seishima, Takeyuki Wada, Kenji Tsuchihashi, Shogo Okazaki, Momoko Yoshikawa, Hiroko Oshima, Masanobu Oshima, Toshiro Sato, Hirotoshi Hasegawa, Yuko Kitagawa, James R. Goldenring, Hideyuki Saya, Osamu Nagano

研究成果: ジャーナルへの寄稿記事

10 引用 (Scopus)

抜粋

Loss of parietal cells initiates the development of spasmolytic polypeptide-expressing metaplasia (SPEM), a precancerous lesion in stomach. CD44 variant (CD44v) that enhances the ability to defend against reactive oxygen species (ROS) in epithelial cells is expressed de novo in SPEM of K19-Wnt1/C2mE mice, a transgenic model of gastric tumorigenesis, and is required for the efficient development of SPEM and gastric tumor in these animals. The role of ROS and its downstream signaling in CD44-dependent gastric tumorigenesis has remained unknown, however. With the use of the K19-Wnt1/C2mE mouse, we now show that parietal cells in the inflamed stomach are highly sensitive to oxidative stress and manifest activation of p38MAPK signaling by ROS. Oral treatment with the antioxidant ascorbic acid or genetic ablation of the Ink4a/Arf locus, a major downstream target of ROS-p38MAPK signaling, inhibited parietal cell loss and the subsequent gastric tumorigenesis. Our results indicate that signaling activated by oxidative stress in parietal cells plays a key role in CD44-dependent gastric tumorigenesis.

元の言語英語
ページ(範囲)492-501
ページ数10
ジャーナルCancer Prevention Research
8
発行部数6
DOI
出版物ステータス出版済み - 6 1 2015
外部発表Yes

    フィンガープリント

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用