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Osterix, a Transcription Factor for Osteoblast Differentiation, Mediates Antitumor Activity in Murine Osteosarcoma

¹ Division of Pediatrics and ² Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Eugenie S. Kleinerman, Division of Pediatrics, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030. Phone: 713-792-8110; Fax: 713-794-5042; E-mail: ekleiner{at}mdanderson.org.

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.

Key Words: osteosarcoma • osterix • osteolysis lesion • lung metastasis • transcription factor

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