P53 mediates interstitial cystitis antiproliferative factor (APF)-induced growth inhibition of human urothelial cells

被引:47
作者
Kim, Jayoung
Keay, Susan K.
Dimitrakov, Jordan D.
Freeman, Michael R.
机构
[1] Childrens Hosp, Urol Dis Res Ctr, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Surg Biol Chem & Mol Pharmacol, Boston, MA 02115 USA
[3] Univ Maryland, Sch Med, Div Infect Dis, Dept Med, Baltimore, MD 21201 USA
[4] VA Med Ctr, Baltimore, MD 21201 USA
关键词
antiproliferative factor; interstitial cystitis; human urothelial cell; p53; p21Cip1/Waf1;
D O I
10.1016/j.febslet.2007.06.058
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Antiproliferative factor (APF) is a sialoglycopeptide elevated in the urine of patients with interstitial cystitis, a urinary bladder disorder of unknown etiology that is characterized by chronic pelvic pain. The present study was directed toward uncovering a pathway through which APF signals. Treatment of human urothelial cells with native APF resulted in growth inhibition accompanied by blockade of cell cycle transit and increased p53. Reduced expression of p53 by RNA interference diminished, while ectopic expression of p53 mimicked, the effects of APF. These are the first findings implicating the network of p53 target genes in urothelial defects associated with interstitial cystitis. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:3795 / 3799
页数:5
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