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The overexpression of bone morphogenetic protein and activin membrane-bound inhibitor and its involvement in the growth and invasion of human osteosarcoma cells

Other Titles
 사람 골육종 세포에서 bone morphogenetic protein and activin membrane-bound inhibitor의 과발현 및 성장과 침습에의 관여 
Authors
 박진 
Issue Date
2013
Description
의학과/박사
Abstract
The pseudoreceptor bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI), formerly known as NMA, is an inhibitor of the TGF-β signaling pathway. BAMBI exhibits structural homology to TGF-βRI but lacks an intracellular kinase domain. In most of the high-grade carcinomas, the degree of BAMBI expression is abnormally increased, which leads to the proliferation and metastasis of tumor cells. Recent studies have reported that the BAMBI is involved in the Wnt-β-catenin pathway that regulates the proliferation and metastasis of tumor cells. However, little is known about the role of BAMBI and β-catenin in human osteosarcoma.Given the above background, we examined the role of BAMBI in the pathophysiology of osteosarcoma. On immunohistochemical staining and western blot analysis, the degree of the expression of BAMBI and β-catenin was significantly higher in osteosarcoma specimen as compared with the normal tissues. With the overexpression of BAMBI, mediated by the adenovirus, the degree of invasion and migration was significantly increased and the proliferation of U2-OS osteosarcoma cells was stimulated. The transwell analysis showed that the BAMBI increased the invasion of osteosarcoma cells and up-regulated the secretion of matrix metalloproteinases (MMPs), which has been demonstrated by gelatin zymography. The fluorescence activated cell sorting (FACS) analysis showed a significant arrest in cell cycle progression at G0/G1 in osteosarcoma cells transinfected with siRNA targeting BMABI. With the overexpression of BAMBI, mediated by the adenovirus, however, there was a decrease in the number of cells at G0/G1. Consistent with the findings that the cell growth was increased, the BAMBI promoted the transition from G0/G1 to G2/M in the osteosarcoma cells.Our results suggest that the BAMBI plays a key role in the pathogenesis and progression of osteosarcoma by regulating the expression of β-catenin and other signaling molecules via the pathways involved in the regulation of the cell cycle. This relationship between the BAMBI and its involvement in the regulation of the cell cycle would provide a possibility that the BAMBI might be a new target for gene therapy
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Orthopedic Surgery (정형외과학교실) > 3. Dissertation
Yonsei Authors
Park, Jin(박진)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/170192
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