Tumor suppressor U19/EAF2 regulates thrombospondin-1 expression via p53

被引:0
作者
F Su
L E Pascal
W Xiao
Z Wang
机构
[1] University of Pittsburgh Cancer Institute,Department of Urology
[2] University of Pittsburgh School of Medicine,Department of Pharmacology and Chemical Biology
[3] Key Laboratory of Biodiversity and Conservation of Aquatic Organisms,undefined
[4] Institute of Hydrobiology,undefined
[5] Chinese Academy of Sciences,undefined
[6] University of Pittsburgh School of Medicine,undefined
[7] 4Current address: Center for Nuclear Receptors and Cell Signaling,undefined
[8] University of Houston,undefined
[9] Houston,undefined
[10] TX 77204,undefined
[11] USA.,undefined
来源
Oncogene | 2010年 / 29卷
关键词
U19/EAF2; prostate cancer; tumor suppressor; TSP-1; p53;
D O I
暂无
中图分类号
学科分类号
摘要
Inactivation of U19/EAF2 has been shown previously to lead to tumorigenesis in multiple organs; however, the mechanism of U19/EAF2 tumor suppression remains unclear. In this paper, we report that the expression of an anti-angiogenic protein, thrombospondin-1 (TSP-1) is down-regulated in the prostate and liver of U19/EAF2 knockout mouse. The U19/EAF2 knockout liver displayed increased CD31-positive blood vessels, suggesting that the TSP-1 down-regulation can contribute to increased angiogenesis. TSP-1 is reported to be a p53-target gene and p53 is a known binding partner of ELL, which binds to U19/EAF2. Here, we show that U19/EAF2 can co-localize and co-immunoprecipitate with p53 in transfected cells. In a TSP-1 promoter-driven luciferase reporter assay, p53 transfection suppressed the TSP-1 promoter activity and U19/EAF2 co-transfection blocked the p53 suppression of TSP-1 promoter. However, U19/EAF2 transfection alone had little or no effect on the TSP-1 promoter. The above observations together suggest that U19/EAF2 regulates the expression of TSP-1 via blocking p53 repression of the TSP-1 promoter.
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页码:421 / 431
页数:10
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共 149 条
[11]  
Dodge RK(2002)Thrombospondin-1, vascular endothelial growth factor expression and their relationship with p53 status in prostate cancer and benign prostatic hyperplasia BJU Int 89 303-309
[12]  
Azam N(1995)Tumour angiogenesis and tumour cell proliferation as prognostic indicators in gastric carcinoma Br J Cancer 72 319-323
[13]  
Vairapandi M(2000)Nonredundant roles of the elongation factor MEN in postimplantation development Biochem Biophys Res Commun 279 563-567
[14]  
Zhang W(2007)Androgen receptor targets NFkappaB and TSP1 to suppress prostate tumor growth Int J Cancer 121 999-1008
[15]  
Hoffman B(2001)The role of hypoxia and p53 in the regulation of angiogenesis in bladder cancer J Urol 165 2075-2081
[16]  
Liebermann DA(2006)Regulation of tumor angiogenesis by thrombospondin-1 Biochim Biophys Acta 1765 178-188
[17]  
Cinatl J(2006)p53 stabilization and transactivation by a von Hippel-Lindau protein Mol Cell 22 395-405
[18]  
Kotchetkov R(1992)Gene targeting using a mouse HPRT minigene/HPRT-deficient embryonic stem cell system: inactivation of the mouse ERCC-1 gene Somat Cell Mol Genet 18 325-336
[19]  
Scholz M(1999)Physical interaction and functional antagonism between the RNA polymerase II elongation factor ELL and p53 J Biol Chem 274 17003-17010
[20]  
Cinatl J(2003)ELL-associated factor 2 (EAF2), a functional homolog of EAF1 with alternative ELL binding properties Blood 101 2355-2362