Thrombospondin-1 is a putative target gene of Runx2 and Runx3.

Abstract

Thrombospondin-1 (TSP-1), a matricellular protein widely acclaimed to be involved in the inhibition of angiogenesis and tumorigenesis, is synthesized and secreted by many cell types, including osteoblast and cancer cells. TSP-1 is highly upregulated during early stage of osteogenesis, whereas it inhibits terminal osteoblast differentiation. Expression of TSP-1 is downregulated in cancer cells, and its ectopic expression has been shown to restrain tumor growth. Transcriptional regulation of TSP-1 in osteogenesis and cancer is poorly understood; this prompted us to study its regulation by the two key regulators of the aforementioned processes: Runx2 and Runx3. Through a PCR-based cDNA subtraction technique, we identified and cloned a cDNA fragment for mouse TSP-1, whose expression was dramatically upregulated in response to Runx2 expression in mesenchymal stem cells. Moreover, TSP-1 expression was considerably reduced in the lung of Runx2 knockout mouse. On the other hand, TSP-1 gene expression drastically increased at both the transcriptional and translational levels in response to Runx3 expression in B16-F10 melanoma cells. In line with this, Runx2 and Runx3 bound to the TSP-1 promoter and stimulated its activity. Hence, these results provide first line of evidence that TSP-1 is a transcriptional target gene of Runx2 and Runx3.

• Authors: Xiuming Shi, Vishwa Deepak, Linghui Wang, Xueqing Ba, Toshihisa Komori, Xianlu Zeng, Wenguang Liu
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 14 Issue 7 Pg. 14321-32 (Jul 10 2013) ISSN: 1422-0067 [Print] Switzerland
• PMID: 23846726 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Core Binding Factor Alpha 1 Subunit
• Core Binding Factor Alpha 3 Subunit
• RNA, Messenger
• Thrombospondin 1

Topics

• Animals
• Base Sequence
• Cell Line, Tumor
• Cell Proliferation
• Core Binding Factor Alpha 1 Subunit (deficiency, genetics, metabolism)
• Core Binding Factor Alpha 3 Subunit (genetics, metabolism)
• Lung (metabolism)
• Mesenchymal Stem Cells (cytology, metabolism)
• Mice
• Mice, Knockout
• Molecular Sequence Data
• Promoter Regions, Genetic
• RNA, Messenger (metabolism)
• Thrombospondin 1 (metabolism)
• Transcription, Genetic