title: 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.affiliation: Institute of Genetics and Cell Biology, Northeast Normal University, Changchun 130024, China. xiumingbio@126.com
authors.forename: Xiuming
authors.initials: X
authors.lastname: Shi
authors.forename: Vishwa
authors.initials: V
authors.lastname: Deepak
authors.forename: Linghui
authors.initials: L
authors.lastname: Wang
authors.forename: Xueqing
authors.initials: X
authors.lastname: Ba
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Komori
authors.forename: Xianlu
authors.initials: X
authors.lastname: Zeng
authors.forename: Wenguang
authors.initials: W
authors.lastname: Liu
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050659:Core Binding Factor Alpha 1 Subunit / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D019700:Thrombospondin 1 / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D012333:RNA, Messenger; D019700:Thrombospondin 1