| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of Medicine and Oncology, McGill University Health Centre, Montreal, Canada
2Correspondence: McGill University Health Centre, 687 Pine Ave. West, Room H4.67, Montreal, Quebec, Canada, H3A 1A1. E-mail: shafaat.rabbani{at}mcgill.ca
Urokinase plasminogen activator (uPA) promotes tumor invasion and metastasis in several malignancies including prostate cancer, one of the most commonly detected male cancers that result in a high incidence of mortality. In the present study we have examined the differential regulation of uPA gene expression in different stages of prostate cancer by DNA methylation. We determined levels of uPA expression in normal prostate epithelial cells (PrEC) and in hormone-responsive (LNCaP) and -insensitive (PC-3) prostate cancer cell lines. We found that uPA is expressed only in the highly invasive PC-3 cells where the uPA promoter is unmethylated. The lack of uPA expression in PrEC and LNCaP cells, where uPA promoter is highly methylated, is due to suppression of uPA gene transcription by DNA methylation. Treatment of LNCaP cells with 5'-azacytidine, a potent demethylating agent, resulted in induction of uPA mRNA expression, uPA activity, and higher invasive capacity in vitro. Additionally, a marked increase in tumor volume was observed after inoculation of these cells into the flank of male BALB/c (nu/nu) mice. Collectively these studies have demonstrated that DNA methylation is the underlying molecular mechanism responsible for uPA gene silencing in normal and early stages of prostate cancer, which has a direct effect on tumor cell invasion and growth in vitro and in vivo.—Pakneshan, P., Xing, R. M., Rabbani, S. A. Methylation status of uPA promoter as a molecular mechanism regulating prostate cancer invasion and growth in vitro and in vivo.
Key Words: urokinase plasminogen activator • CpG dinucleotides • MSP
This article has been cited by other articles:
|
|
 |
|
  T M Murphy, A S Perry, and M Lawler The emergence of DNA methylation as a key modulator of aberrant cell death in prostate cancer Endocr. Relat. Cancer, March 1, 2008; 15(1): 11 - 25. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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. Milutinovic, A. C. D'Alessio, N. Detich, and M. Szyf Valproate induces widespread epigenetic reprogramming which involves demethylation of specific genes Carcinogenesis, March 1, 2007; 28(3): 560 - 571. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. K. Pulukuri, N. Estes, J. Patel, and J. S. Rao Demethylation-Linked Activation of Urokinase Plasminogen Activator Is Involved in Progression of Prostate Cancer Cancer Res., February 1, 2007; 67(3): 930 - 939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Shukeir, P. Pakneshan, G. Chen, M. Szyf, and S. A. Rabbani Alteration of the Methylation Status of Tumor-Promoting Genes Decreases Prostate Cancer Cell Invasiveness and Tumorigenesis In vitro and In vivo. Cancer Res., September 15, 2006; 66(18): 9202 - 9210. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S Perry, R. Foley, K. Woodson, and M. Lawler The emerging roles of DNA methylation in the clinical management of prostate cancer. Endocr. Relat. Cancer, June 1, 2006; 13(2): 357 - 377. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. WANG, J. HAYAKAWA, F. LONG, Q. YU, A. H. CHO, G. RONDEAU, J. WELSH, S. MITTAL, I. DE BELLE, E. ADAMSON, et al. "Promoter Array" Studies Identify Cohorts of Genes Directly Regulated by Methylation, Copy Number Change, or Transcription Factor Binding in Human Cancer Cells Ann. N.Y. Acad. Sci., November 1, 2005; 1058(1): 162 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Pulukuri, C. S. Gondi, S. S. Lakka, A. Jutla, N. Estes, M. Gujrati, and J. S. Rao RNA Interference-directed Knockdown of Urokinase Plasminogen Activator and Urokinase Plasminogen Activator Receptor Inhibits Prostate Cancer Cell Invasion, Survival, and Tumorigenicity in Vivo J. Biol. Chem., October 28, 2005; 280(43): 36529 - 36540. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D M Peehl Primary cell cultures as models of prostate cancer development Endocr. Relat. Cancer, March 1, 2005; 12(1): 19 - 47. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Pakneshan, M. Szyf, and S. A. Rabbani Methylation and inhibition of expression of uPA by the RAS oncogene: divergence of growth control and invasion in breast cancer cells Carcinogenesis, March 1, 2005; 26(3): 557 - 564. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-C. Li, P. R. Carroll, and R. Dahiya Epigenetic Changes in Prostate Cancer: Implication for Diagnosis and Treatment J Natl Cancer Inst, January 19, 2005; 97(2): 103 - 115. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Pakneshan, M. Szyf, R. Farias-Eisner, and S. A. Rabbani Reversal of the Hypomethylation Status of Urokinase (uPA) Promoter Blocks Breast Cancer Growth and Metastasis J. Biol. Chem., July 23, 2004; 279(30): 31735 - 31744. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Benasciutti, G. Pages, O. Kenzior, W. Folk, F. Blasi, and M. P. Crippa MAPK and JNK transduction pathways can phosphorylate Sp1 to activate the uPA minimal promoter element and endogenous gene transcription Blood, July 1, 2004; 104(1): 256 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pakneshan, B. Tetu, and S. A. Rabbani Demethylation of Urokinase Promoter as a Prognostic Marker in Patients with Breast Carcinoma Clin. Cancer Res., May 1, 2004; 10(9): 3035 - 3041. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
