Regulation of prostasin expression and function in the prostate

    Authors

    L. M. Chen; X. C. Zhang;K. X. Chai

    Comments

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    Abbreviated Journal Title

    Prostate

    Keywords

    serine protease; serpin; protease nexin-1; invasion suppressor; DNA; methylation; NERVE GROWTH-FACTOR; CANCER CELLS; SERINE-PROTEASE; EPITHELIAL-CELLS; TUMOR-SUPPRESSOR; GENE-EXPRESSION; PC12 CELLS; SERPIN; MASPIN; NEXIN; Endocrinology & Metabolism; Urology & Nephrology

    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 DU-145 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. (C) 2003 Wiley-Liss, Inc.

    Journal Title

    Prostate

    Volume

    59

    Issue/Number

    1

    Publication Date

    1-1-2004

    Document Type

    Article

    Language

    English

    First Page

    1

    Last Page

    12

    WOS Identifier

    WOS:000220392400001

    ISSN

    0270-4137

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