Title

Regulation Of Prostasin Expression And Function In The Prostate

Keywords

DNA methylation; Invasion suppressor; Protease nexin-1; Serine protease; Serpin

Abstract

BACKGROUND. The invasion suppressor prostasin is down-regulated in prostate cancer, but the mechanism is unknown. A prostasin-binding protein (PBP) was found in the seminal vesicles, but its identity remains unclear. METHODS. Genomic Southern blot analysis using methylation sensitive restriction endonucleases was employed to examine the prostasin gene promoter region in prostate cancer cell lines. RT-PCR was employed to examine prostasin expression under demethylation, histone deacetylase inhibition, and nerve growth factor (NGF) treatment. Liquid column chromatography was employed to purify the PBP from mouse seminal vesicles. The PBP was further characterized by amino acid sequence analysis, recombinant protein expression, protease inhibition and binding assays. Immunohistochemistry and Western blot analysis were used to evaluate PBP expression in the prostate and prostate cancer cells. RESULTS. Promoter DNA methylation partly causes the prostasin down-regulation in DU145 and PC-3 cells, while prostasin expression can be induced by NGF. The PBP is identified to be protease nexin-1 (PN-1), a serpin. PN-1 inhibits prostasin's serine protease activity, is expressed by prostate epithelial cells (PrECs) and prostate cancer cells, and capable of binding to membrane-anchored prostasin. CONCLUSIONS. Prostasin's expression and function are regulated by factors in the prostate tissue environment. © 2003 Wiley-Liss, Inc.

Publication Date

4-1-2004

Publication Title

Prostate

Volume

59

Issue

1

Number of Pages

1-12

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1002/pros.10346

Socpus ID

1642326652 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/1642326652

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