Osterix, a transcription factor for osteoblast differentiation, mediates antitumor activity in murine osteosarcoma.
Osterix is a novel zinc finger-containing transcription factor that is essential for osteoblast differentiation and bone formation. We hypothesized that osterix might have a role in osteosarcoma tumor growth and metastasis. Northern blot analysis showed that the mRNA level of osterix was decreased in two mouse osteosarcoma cell lines compared with its level in normal mouse osteoblasts. Osterix expression was also decreased in three human osteosarcoma cell lines. Transfection of the osx gene into the mouse osteosarcoma cells inhibited tumor cell growth in vitro and in vivo and significantly reduced tumor incidence, tumor volume, and lung metastasis following intratibial injection. Osterix expression was also associated with decreased osteolysis. Using an in vitro migration assay, osterix suppressed the migration of tumor cells to lung extracts. These results suggest that osterix expression may play a role in osteosarcoma tumor growth and metastasis.
Cao
Ying
Y
Division of Pediatrics and Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
Zhou
Zhichao
Z
de Crombrugghe
Benoit
B
Nakashima
Kazuhisa
K
Guan
Hui
H
Duan
Xiaoping
X
Jia
Shu-Fang
SF
Kleinerman
Eugenie S
ES
D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D002454:Cell Differentiation / Q000502:physiology; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D015536:Down-Regulation; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors; D051379:Mice; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014162:Transfection
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D014157:Transcription Factors