title: Bone morphogenetic protein-2 and -4 play tumor suppressive roles in human diffuse-type gastric carcinoma.
abstract: A relationship exists between defects in bone morphogenetic protein (BMP) signaling and formation of hamartoma and adenoma in the gastric epithelium; however, the role of BMP signaling in the progression of diffuse-type gastric carcinoma remains unknown. We investigated whether BMP functions as a tumor suppressor in human diffuse-type gastric carcinoma using three different human diffuse-type gastric carcinoma cell lines (OCUM-12, HSC-39, and OCUM-2MLN). Overexpression of the dominant-negative form of BMP-2/4-specific type I receptor (ALK-3) in OCUM-12 and HSC-39 cells accelerated their growth in vivo. BMP-4 induced cell cycle arrest in these cells via p21 induction through the SMAD pathway. Moreover, overexpression of the constitutively active form of ALK-3 in HSC-39 and OCUM-2MLN cells suppressed the proliferation of these cells in vitro and in vivo. Our findings suggest that BMP-2 and BMP-4 function as potent tumor suppressors in diffuse-type gastric carcinoma.
authors: Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Yo-taro
authors: YT
authors: Shirai
authors: Shogo
authors: S
authors: Ehata
authors: Masakazu
authors: M
authors: Yashiro
authors: Kazuyoshi
authors: K
authors: Yanagihara
authors: Kosei
authors: K
authors: Hirakawa
authors: Kohei
authors: K
authors: Miyazono
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism / Q000502:physiology*; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism / Q000502:physiology*; D052004:Bone Morphogenetic Protein Receptors / Q000378:metabolism; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D018450:Disease Progression; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010766:Phosphorylation; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051785:Smad Proteins / Q000378:metabolism; D013274:Stomach Neoplasms / Q000209:etiology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C498212:Bmpr1a protein, mouse; D052004:Bone Morphogenetic Protein Receptors; D052005:Bone Morphogenetic Protein Receptors, Type I