BMP-2 modulates the proliferation and differentiation of normal and cancerous gastric cells.
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.
Department of Molecular Oncology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Xian-Zi
XZ
Wen
Satoshi
S
Miyake
Yoshimitsu
Y
Akiyama
Yasuhito
Y
Yuasa
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D055396:Bone Morphogenetic Protein 2; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D016193:G1 Phase / Q000187:drug effects; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D020116:Pepsinogen A / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017978:Receptors, Growth Factor / Q000378:metabolism; D011994:Recombinant Proteins; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta; D015854:Up-Regulation
D000970:Antineoplastic Agents; C525718:BMP2 protein, human; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; C493956:CDKN1A protein, human; C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D006131:Growth Inhibitors; D017978:Receptors, Growth Factor; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D020116:Pepsinogen A; D052004:Bone Morphogenetic Protein Receptors