Bone morphogenetic protein-2 and -4 play tumor suppressive roles in human diffuse-type gastric carcinoma
| Autor: | Kosei Hirakawa, Kazuyoshi Yanagihara, Shogo Ehata, Masakazu Yashiro, Kohei Miyazono, Yo-taro Shirai |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Cell cycle checkpoint Bone Morphogenetic Protein 2 Mice Nude Smad Proteins SMAD Bone Morphogenetic Protein 4 Biology Bone morphogenetic protein Bone morphogenetic protein 2 Pathology and Forensic Medicine Mice Stomach Neoplasms Transforming Growth Factor beta Cell Line Tumor Animals Bone morphogenetic protein receptor Phosphorylation Bone Morphogenetic Protein Receptors Type I Cell Proliferation Mice Inbred BALB C Cell growth Regular Article Bone Morphogenetic Protein Receptors Cell Cycle Checkpoints BMPR2 Cell culture Cancer research Disease Progression Receptors Transforming Growth Factor beta Signal Transduction |
| Zdroj: | The American journal of pathology. 179(6) |
| ISSN: | 1525-2191 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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