This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pulukuri, S. M. K. Articles by Rao, J. S. Search for Related Content PubMed PubMed Citation Articles by Pulukuri, S. M. K. Articles by Rao, J. S.

Demethylation-Linked Activation of Urokinase Plasminogen Activator Is Involved in Progression of Prostate Cancer

Departments of ¹ Cancer Biology and Pharmacology, ² Surgery, ³ Pathology, and ⁴ Neurosurgery, University of Illinois College of Medicine at Peoria, Peoria, Illinois

Requests for reprints: Jasti S. Rao, Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Box 1649, Peoria, IL 61656. Phone: 309-671-3445; E-mail: jsrao{at}uic.edu.

Increased expression of urokinase plasminogen activator (uPA) has been reported in various malignancies including prostate cancer. However, the mechanism by which uPA is abnormally expressed in prostate cancer remains elusive. Here, we show that uPA is aberrantly expressed in a high percentage of human prostate cancer tissues but rarely expressed either in tumor-matched nonneoplastic adjacent tissues or benign prostatic hyperplasia samples. This aberrant expression is associated with cancer-linked demethylation of the uPA promoter. Furthermore, treatment with demethylation inhibitor S-adenosylmethionine or stable expression of uPA short hairpin RNA significantly inhibits uPA expression and tumor cell invasion in vitro and tumor growth and incidence of lung metastasis in vivo. Collectively, these findings strongly suggest that DNA demethylation is a common mechanism underlying the abnormal expression of uPA and is a critical contributing factor to the malignant progression of human prostate tumors. [Cancer Res 2007;67(3):930–9]

This article has been cited by other articles:

				S. M. K. Pulukuri, B. Gorantla, and J. S. Rao Inhibition of Histone Deacetylase Activity Promotes Invasion of Human Cancer Cells through Activation of Urokinase Plasminogen Activator J. Biol. Chem., December 7, 2007; 282(49): 35594 - 35603. [Abstract] [Full Text] [PDF]

				S. M. K. Pulukuri and J. S. Rao Small Interfering RNA Directed Reversal of Urokinase Plasminogen Activator Demethylation Inhibits Prostate Tumor Growth and Metastasis Cancer Res., July 15, 2007; 67(14): 6637 - 6646. [Abstract] [Full Text] [PDF]