Eliseev R A, Dong Y-F, Sampson E, Zuscik M J, Schwarz E M, O'Keefe R J, Rosier R N, Drissi M H
Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA.
Oncogene. 2008 Jun 5;27(25):3605-14. doi: 10.1038/sj.onc.1211020. Epub 2008 Jan 28.
The Runx family of transcription factors regulate cell growth and differentiation, and control the expression of target genes involved in cell fate decisions. We examined the role of the bone-related member of this family, Runx2, in regulating apoptosis via modulation of the Bcl2 family of genes in the osteosarcoma cell line Saos2. Our data demonstrate that Runx2 directly binds to two Runx-specific regulatory elements on the human bax promoter thereby inducing Bax expression. Furthermore, bone morphogenetic protein-induced or vector-mediated expression of Runx2 resulted in upregulation of Bax expression, and subsequent increased sensitivity of Saos2 cells to apoptosis. Finally, the observed upregulation of Bax expression and increased apoptosis were Runx2 dependent as Runx2 loss of function abrogated these effects. Our study provides the first evidence for Bax as a direct target of Runx2, suggesting that Runx2 may act as a proapoptotic factor in osteosarcoma cells.
Runx转录因子家族调控细胞生长和分化，并控制参与细胞命运决定的靶基因的表达。我们研究了该家族与骨相关的成员Runx2在骨肉瘤细胞系Saos2中通过调节Bcl2基因家族来调控细胞凋亡的作用。我们的数据表明，Runx2直接结合到人bax启动子上的两个Runx特异性调控元件，从而诱导Bax表达。此外，骨形态发生蛋白诱导的或载体介导的Runx2表达导致Bax表达上调，随后Saos2细胞对细胞凋亡的敏感性增加。最后，观察到的Bax表达上调和细胞凋亡增加是Runx2依赖性的，因为Runx2功能丧失消除了这些效应。我们的研究首次证明Bax是Runx2的直接靶点，表明Runx2可能在骨肉瘤细胞中作为促凋亡因子发挥作用。
