Causal relationship between the loss of RUNX3 expression and gastric cancer.
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.
Li
Qing Lin
QL
Department of Biochemistry, College of Medicine, Institute of Medical Research, Chungbuk National University, 361-763, Cheongju, South Korea.
Ito
Kosei
K
Sakakura
Chohei
C
Fukamachi
Hiroshi
H
Inoue
Ken ichi
Ki
Chi
Xin Zi
XZ
Lee
Kwang Youl
KY
Nomura
Shintaro
S
Lee
Chang Woo
CW
Han
Sang Bae
SB
Kim
Hwan Mook
HM
Kim
Wun Jae
WJ
Yamamoto
Hiromitsu
H
Yamashita
Namiko
N
Yano
Takashi
T
Ikeda
Toshio
T
Itohara
Shigeyoshi
S
Inazawa
Johji
J
Abe
Tatsuo
T
Hagiwara
Akeo
A
Yamagishi
Hisakazu
H
Ooe
Asako
A
Kaneda
Atsushi
A
Sugimura
Takashi
T
Ushijima
Toshikazu
T
Bae
Suk Chul
SC
Ito
Yoshiaki
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002455:Cell Division / Q000187:drug effects / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D050677:Core Binding Factor Alpha 3 Subunit; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D004848:Epithelium / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005091:Exons / Q000235:genetics; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D018390:Gene Targeting; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017434:Protein Structure, Tertiary / Q000235:genetics; D013270:Stomach / Q000473:pathology / Q000503:physiopathology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000172:deficiency* / Q000235:genetics
D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins; C493729:Runx3 protein, human; C493730:Runx3 protein, mouse; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins