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 G(1)-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. (C) 2004 Elsevier Inc. All rights reserved.