TY - JOUR
T1 - CCAAT/enhancer binding protein beta is up-regulated in giant cell tumor of bone and regulates RANKL expression
AU - Ng, Patrick Kwok Shing
AU - Tsui, Stephen Kwok Wing
AU - Lau, Carol Po Ying
AU - Wong, Chi Hang
AU - Wong, Winnie Hiu Ting
AU - Huang, Lin
AU - Kumta, Shekhar Madhukar
PY - 2010/5/15
Y1 - 2010/5/15
N2 - Giant cell tumor (GCT) of bone is an aggressive non-cancerous tumor, which consists of multi-nucleated osteoclast-like giant cells, stromal cells, and monocytes. It is believed that stromal cells are the neoplastic component of this tumor. Expression of the receptor activator of nuclear factor kappa B ligand (RANKL) in the stromal cells stimulates the monocytes to form giant multi-nucleated osteoclast-like cells, causing bone over-resorption at the tumor site. Previously, our group has reported the up-regulation of RANKL in GCT of bone stromal cells, but the mechanism is unknown. Using stromal cell culture of GCT obtained from patients, we demonstrated the up-regulation of the transcriptional activator CCAAT/enhancer binding protein beta (C/EBPβ). RANKL promoter studies revealed that C/EBPb over-expression induced RANKL promoter activity in a dose-dependent manner and a CCAAT-box within the region nt -357/-1 contributed to the basal transcription activity, with a possible C/EBPβ binding element in the region nt -460/-358 leading to further induction. Furthermore, we also showed that C/EBPβ bound to the RANKL promoter in GCT stromal cells in vivo by chromatin immunoprecipitation. To conclude, our study has shown that C/EBPβ is a RANKL promoter activator in stromal cells of GCT of bone and we have proposed a model in which C/EBPb plays an important role in the osteolytic characteristics and pathological causes of GCT of bone.
AB - Giant cell tumor (GCT) of bone is an aggressive non-cancerous tumor, which consists of multi-nucleated osteoclast-like giant cells, stromal cells, and monocytes. It is believed that stromal cells are the neoplastic component of this tumor. Expression of the receptor activator of nuclear factor kappa B ligand (RANKL) in the stromal cells stimulates the monocytes to form giant multi-nucleated osteoclast-like cells, causing bone over-resorption at the tumor site. Previously, our group has reported the up-regulation of RANKL in GCT of bone stromal cells, but the mechanism is unknown. Using stromal cell culture of GCT obtained from patients, we demonstrated the up-regulation of the transcriptional activator CCAAT/enhancer binding protein beta (C/EBPβ). RANKL promoter studies revealed that C/EBPb over-expression induced RANKL promoter activity in a dose-dependent manner and a CCAAT-box within the region nt -357/-1 contributed to the basal transcription activity, with a possible C/EBPβ binding element in the region nt -460/-358 leading to further induction. Furthermore, we also showed that C/EBPβ bound to the RANKL promoter in GCT stromal cells in vivo by chromatin immunoprecipitation. To conclude, our study has shown that C/EBPβ is a RANKL promoter activator in stromal cells of GCT of bone and we have proposed a model in which C/EBPb plays an important role in the osteolytic characteristics and pathological causes of GCT of bone.
KW - C/EBPβ
KW - Giant cell tumor of bone
KW - Promoter analysis
KW - RANKL
KW - Stromal cells
UR - http://www.scopus.com/inward/record.url?scp=77952017371&partnerID=8YFLogxK
U2 - 10.1002/jcb.22556
DO - 10.1002/jcb.22556
M3 - Article
C2 - 20225273
AN - SCOPUS:77952017371
SN - 0730-2312
VL - 110
SP - 438
EP - 446
JO - Journal of Cellular Biochemistry
JF - Journal of Cellular Biochemistry
IS - 2
ER -