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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / drug effects
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Apoptosis / genetics
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Cell Division / drug effects
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Cell Division / genetics*
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Cell Transformation, Neoplastic / drug effects
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Cell Transformation, Neoplastic / genetics*
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Core Binding Factor Alpha 3 Subunit
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DNA Methylation
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DNA-Binding Proteins / deficiency*
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DNA-Binding Proteins / genetics
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Epithelium / metabolism*
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Epithelium / pathology
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Epithelium / physiopathology
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Exons / genetics
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Female
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Gastric Mucosa / metabolism*
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Gene Deletion
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Gene Expression Regulation, Neoplastic / drug effects
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Gene Expression Regulation, Neoplastic / genetics
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Gene Targeting
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Humans
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Hyperplasia / genetics
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Hyperplasia / pathology
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Hyperplasia / physiopathology
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Male
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Mice
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Mice, Knockout
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Protein Structure, Tertiary / genetics
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Stomach / pathology
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Stomach / physiopathology
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Stomach Neoplasms / genetics*
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Stomach Neoplasms / metabolism
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Stomach Neoplasms / physiopathology
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Transcription Factors / deficiency*
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Transcription Factors / genetics
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Transforming Growth Factor beta / metabolism
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Transforming Growth Factor beta / pharmacology
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Tumor Cells, Cultured
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Tumor Suppressor Proteins / deficiency*
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Tumor Suppressor Proteins / genetics
Substances
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Core Binding Factor Alpha 3 Subunit
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DNA-Binding Proteins
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Runx3 protein, human
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Runx3 protein, mouse
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Transcription Factors
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Transforming Growth Factor beta
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Tumor Suppressor Proteins