Down-regulation of prostasin serine protease: A potential invasion suppressor in prostate cancer

• Published in: The Prostate Vol. 48; no. 2; pp. 93 - 103
• Main Authors: Chen, Li-Mei, Hodge, G. Byron, Guarda, Luis A., Welch, James L., Greenberg, Norman M., Chai, Karl X.
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.07.2001; Wiley-Liss
• Subjects: Biological and medical sciences; Blotting, Western; cell line; DNA, Complementary; Down-Regulation; gene expression; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Male; Medical sciences; Neoplasm Invasiveness; Nephrology. Urinary tract diseases; prostatectomy; Prostatic Neoplasms - pathology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; Serine Endopeptidases - biosynthesis; Serine Endopeptidases - pharmacology; Transfection; Tumor Cells, Cultured; Tumors of the urinary system; Urinary tract. Prostate gland; Human; Immunohistochemistry; Pathology; Regulation(control); Urinary system disease; Cell line; Prostate disease; Biological marker; Malignant tumor; Male genital diseases; In vitro; Prostate
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.1085

BACKGROUND Prostasin is a serine protease predominantly expressed in normal prostate epithelial cells. The biological function of prostasin has not been determined. METHODS Western blot and RT‐PCR analyses were used to examine the expression of prostasin in prostate cancer cell lines. Immunohistochemistry was used to evaluate prostasin protein expression in human prostate cancer. An in vitro Matrigel invasion assay was used to test the invasiveness of prostate cancer cell lines forced to express recombinant prostasin. RESULTS Both prostasin protein and mRNA were found to be expressed in normal human prostate epithelial cells and a non‐invasive human prostate cancer cell line, the LNCaP, but neither was found in invasive human prostate cancer cell lines DU‐145 and PC‐3. Prostasin mRNA expression was absent in invasive prostate cancer cell lines of a transgenic mouse model. Immunohistochemistry analysis showed that prostasin protein expression is down‐regulated in high‐grade prostate cancer. Transfection of DU‐145 and PC‐3 cells with a full‐length human prostasin cDNA restored prostasin expression and reduced the in vitro invasiveness by 68 and 42%, respectively. CONCLUSIONS Our data indicate that prostasin may be implicated in normal prostate biology and is able to suppress prostate cancer invasion in vitro. Prostate 48:93–103, 2001. © 2001 Wiley‐Liss, Inc.