Abstract
Bone morphogenetic protein 2 (BMP-2), a member of the transforming growth factor beta super-family, has been shown to act as an antiproliferative agent for a variety of cell lines by activating signaling cascades that cause cell cycle arrest. However, the biological effect and mechanism of action of BMP-2 on gastric cells remain unknown. In the present study, we showed that recombinant human BMP-2 dose-dependently inhibited the growth of OUMS37 rat gastric cells and MKN74 human gastric cancer cells. The antiproliferation seems to be due to cell cycle arrest in the G1-phase, which was revealed by flow cytometric assays. BMP-2 increased the level of p21/WAF1/CIP1, suggesting that BMP-2-mediated inhibition of cell proliferation may be induced through p21/WAF1/CIP1. In addition, BMP-2 increased the expression of pepsinogen II, a differentiation marker of the stomach, in MKN74 cells. These results indicate that BMP-2 plays important roles in modulating the proliferation and differentiation of gastric epithelial cells.
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology*
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Protein Receptors
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Bone Morphogenetic Proteins / pharmacology*
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Cell Differentiation / drug effects
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Cell Division / drug effects
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Cell Line
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Cell Line, Tumor
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins / biosynthesis
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Cyclins / genetics
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G1 Phase / drug effects
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Gastric Mucosa / cytology
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Gastric Mucosa / drug effects*
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Gastric Mucosa / metabolism
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Growth Inhibitors / pharmacology*
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Humans
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Pepsinogen A / biosynthesis
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Pepsinogen A / genetics
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Rats
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Receptors, Growth Factor / metabolism
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Recombinant Proteins
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Stomach Neoplasms / genetics
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Stomach Neoplasms / metabolism*
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Stomach Neoplasms / pathology
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Transforming Growth Factor beta*
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Up-Regulation
Substances
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Antineoplastic Agents
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BMP2 protein, human
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Bmp2 protein, rat
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Proteins
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CDKN1A protein, human
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Cdkn1a protein, rat
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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Growth Inhibitors
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Receptors, Growth Factor
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Recombinant Proteins
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Transforming Growth Factor beta
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recombinant human bone morphogenetic protein-2
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Pepsinogen A
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Bone Morphogenetic Protein Receptors