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CCAAT/enhancer binding protein beta is up‐regulated in giant cell tumor of bone and regulates RANKL expression
Author(s) -
Ng Patrick KwokShing,
Tsui Stephen KwokWing,
Lau Carol PoYing,
Wong ChiHang,
Wong Winnie HiuTing,
Huang Lin,
Kumta ShekharMadhukar
Publication year - 2010
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22556
Subject(s) - rankl , stromal cell , osteoclast , giant cell tumor of bone , cancer research , ccaat enhancer binding proteins , microbiology and biotechnology , activator (genetics) , chemistry , transcription factor , biology , giant cell , receptor , medicine , nuclear protein , gene , biochemistry , genetics
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/EBPβ 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/EBPβ plays an important role in the osteolytic characteristics and pathological causes of GCT of bone. J. Cell. Biochem. 110: 438–446, 2010. © 2010 Wiley‐Liss, Inc.