2. Academic Validation
  3. Causal relationship between the loss of RUNX3 expression and gastric cancer

Causal relationship between the loss of RUNX3 expression and gastric cancer

  • Cell. 2002 Apr 5;109(1):113-24. doi: 10.1016/s0092-8674(02)00690-6.
Qing Lin Li 1,  Kosei Ito,  Chohei Sakakura,  Hiroshi Fukamachi,  Ken ichi Inoue,  Xin Zi Chi,  Kwang Youl Lee,  Shintaro Nomura,  Chang Woo Lee,  Sang Bae Han,  Hwan Mook Kim,  Wun Jae Kim,  Hiromitsu Yamamoto,  Namiko Yamashita,  Takashi Yano,  Toshio Ikeda,  Shigeyoshi Itohara,  Johji Inazawa,  Tatsuo Abe,  Akeo Hagiwara,  Hisakazu Yamagishi,  Asako Ooe,  Atsushi Kaneda,  Takashi Sugimura,  Toshikazu Ushijima,  Suk Chul Bae,  Yoshiaki Ito
Affiliations

Affiliation

  • 1 Department of Biochemistry, College of Medicine, Institute of Medical Research, Chungbuk National University, 361-763, Cheongju, South Korea.
PMID: 11955451 DOI: 10.1016/s0092-8674(02)00690-6
Abstract

Runx3/Pebp2alphaC null mouse gastric mucosa exhibits hyperplasias due to stimulated proliferation and suppressed Apoptosis in epithelial cells, and the cells are resistant to growth-inhibitory and apoptosis-inducing action of TGF-beta, indicating that Runx3 is a major growth regulator of gastric epithelial cells. Between 45% and 60% of human gastric Cancer cells do not significantly express RUNX3 due to hemizygous deletion and hypermethylation of the RUNX3 promoter region. Tumorigenicity of human gastric Cancer cell lines in nude mice was inversely related to their level of RUNX3 expression, and a mutation (R122C) occurring within the conserved Runt domain abolished the tumor-suppressive effect of RUNX3, suggesting that a lack of RUNX3 function is causally related to the genesis and progression of human gastric Cancer.

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