BMP-2 modulates the proliferation and differentiation of normal and cancerous gastric cells

• DOI: 10.1016/j.bbrc.2004.02.016
• Publication Date: 2004-03-09T13:52:41Z
• Authors: Xian-Zi Wen; Satoshi Miyake; Yoshimitsu Akiyama; Yasuhito Yuasa
• Keywords: Cyclin-Dependent Kinase Inhibitor p21; 0301 basic medicine; G1 Phase; Bone Morphogenetic Protein 2; Antineoplastic Agents; Cell Differentiation; Bone Morphogenetic Protein Receptors; Growth Inhibitors; Recombinant Proteins; Cell Line; Rats; 3. Good health; 03 medical and health sciences; Gastric Mucosa; Stomach Neoplasms; Cell Line, Tumor; Cyclins; Pepsinogen A; Bone Morphogenetic Proteins; Animals; Humans; Receptors, Growth Factor; Cell Division

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.