Keywords

Prostasin, GPI-anchor, BPH, Invasion

Abstract

Prostasin is expressed in normal prostate epithelial cells but down-regulated in prostate cancers, while prostasin re-expression in invasive prostate cancer cells reduced invasion. We examined prostasin expression and function in benign prostatic hyperplasia (BPH). We evaluated prostasin expression in 12 BPH specimens by immunohistochemistry, and evaluated the impact of prostasin silencing by siRNA on the expression of the inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), and cyclin D1, as well as on cell proliferation and invasion, using the BPH-1 human prostate epithelial cell line model. Prostasin expression was localized in the glands of BPH tissues by immunohistochemistry, in either the tall columnar-shaped or the flattened epithelial cells. We silenced prostasin expression by >50% at both the mRNA and protein levels using siRNA in the BPH-1 human prostate epithelial cell line, and this silencing of prostasin expression was associated with an induction of iNOS and ICAM-1 expression and a down-regulation of cyclin D1 expression. The protein expression of EGFR, a putative prostasin substrate, was not affected by prostasin silencing in this cell line. The prostasin-silenced cells displayed a reduced cell proliferation rate and reduced invasiveness, cell behaviors regulated by cyclin D1, iNOS, and ICAM-1 in the BPH-1 cells. We believe that this down-regulation of cyclin D1 is due to prostasin's augmentative effect on iNOS. We also believe that the decrease in cell motility is due to an increase in iNOS and ICAM-1 as well as a decrease in cyclin D1, since all of these molecules can play a role in cell motility. In conclusion, Prostasin is somehow involved in the regulation of inflammatory gene expression (iNOS and ICAM-1) in prostate epithelial cells, as well as cyclin D1 expression, cell proliferation and invasion, involving molecular mechanisms different than those in the prostate cancer cells. These studies suggest that prostasin is a player in the glandular components of benign prostatic hyperplasia.

Notes

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Graduation Date

2008

Advisor

Chai, Karl

Degree

Master of Science (M.S.)

College

Burnett College of Biomedical Sciences

Department

Molecular Biology and Microbiology

Degree Program

Molecular and Microbiology

Format

application/pdf

Identifier

CFE0002190

URL

http://purl.fcla.edu/fcla/etd/CFE0002190

Language

English

Release Date

September 2008

Length of Campus-only Access

None

Access Status

Masters Thesis (Open Access)

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