Runx2-mediated activation of the Bax gene increases osteosarcoma cell sensitivity to apoptosis

• Published in: Oncogene Vol. 27; no. 25; pp. 3605 - 3614
• Main Authors: Eliseev, R A, Dong, Y-F, Sampson, E, Zuscik, M J, Schwarz, E M, O'Keefe, R J, Rosier, R N, Drissi, M H
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.06.2008; Nature Publishing; Nature Publishing Group
• Subjects: Ageing, cell death; Apoptosis; BAX gene; bcl-2-Associated X Protein - metabolism; Biological and medical sciences; Bone cancer; Bone Neoplasms - metabolism; Caspase 3 - metabolism; Cbfa-1 protein; Cell Biology; Cell differentiation; Cell fate; Cell Line, Tumor; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Core Binding Factor Alpha 1 Subunit - physiology; Diseases of the osteoarticular system; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Genetic aspects; Human Genetics; Humans; Internal Medicine; Medical sciences; Medicine; Medicine & Public Health; Models, Biological; Molecular and cellular biology; Mutagenesis, Site-Directed; Oncology; original-article; Osteosarcoma; Osteosarcoma - metabolism; Osteosarcoma cells; Promoter Regions, Genetic; Proteins; Regulatory sequences; Risk factors; Sarcoma; Transcription factors; Transcriptional Activation; Tumors of striated muscle and skeleton; United States; Bax; apoptosis; osteosarcoma; Runx2; Sarcoma; Diseases of the osteoarticular system; Activation; Malignant tumor; Carcinogenesis; Osteoarticular system; Sensitivity; Gene; Osteosarcoma; Bone; Cancer; Apoptosis
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1211020

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.