title: Causal relationship between the loss of RUNX3 expression and gastric cancer.
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.
authors.affiliation: Department of Biochemistry, College of Medicine, Institute of Medical Research, Chungbuk National University, 361-763, Cheongju, South Korea.
authors.forename: Qing Lin
authors.initials: QL
authors.lastname: Li
authors.forename: Kosei
authors.initials: K
authors.lastname: Ito
authors.forename: Chohei
authors.initials: C
authors.lastname: Sakakura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukamachi
authors.forename: Ken ichi
authors.initials: Ki
authors.lastname: Inoue
authors.forename: Xin Zi
authors.initials: XZ
authors.lastname: Chi
authors.forename: Kwang Youl
authors.initials: KY
authors.lastname: Lee
authors.forename: Shintaro
authors.initials: S
authors.lastname: Nomura
authors.forename: Chang Woo
authors.initials: CW
authors.lastname: Lee
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Han
authors.forename: Hwan Mook
authors.initials: HM
authors.lastname: Kim
authors.forename: Wun Jae
authors.initials: WJ
authors.lastname: Kim
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Namiko
authors.initials: N
authors.lastname: Yamashita
authors.forename: Takashi
authors.initials: T
authors.lastname: Yano
authors.forename: Toshio
authors.initials: T
authors.lastname: Ikeda
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Abe
authors.forename: Akeo
authors.initials: A
authors.lastname: Hagiwara
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Yamagishi
authors.forename: Asako
authors.initials: A
authors.lastname: Ooe
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kaneda
authors.forename: Takashi
authors.initials: T
authors.lastname: Sugimura
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Ushijima
authors.forename: Suk Chul
authors.initials: SC
authors.lastname: Bae
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ito
mesh_terms: 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
chemical_list: 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