Up-regulation of cathepsin X in prostate cancer and prostatic intraepithelial neoplasia.

Abstract

BACKGROUND:

Evidence is accumulating that several proteases are involved in prostate cancer progression. A locus which is often amplified in prostate cancer is the chromosomal region 20q13. Interestingly, one of the genes encoding the cysteine protease cathepsin X maps to this region. The aim of this study was to assess the expression pattern of cathepsin X in malignant and non-malignant prostatic tissue samples.

METHODS:

Matched malignant and non-malignant tissue specimens were obtained from 56 men after radical prostatectomy. Cathepsin X was quantified at both protein and mRNA levels using several detection methods: Western blotting, immunohistochemistry, quantitative RT-PCR, and in situ hybridization. Furthermore, genomic DNA was analyzed by PCR for possible gene amplification.

RESULTS:

Immunohistochemical analysis of formalin-fixed, paraffin-embedded sections of radical prostatectomy specimens was performed utilizing a polyclonal antibody against human procathepsin X and revealed staining of acinar basal cells in normal prostate glands. Prostatic intraepithelial neoplasias (PINs) and prostate carcinomas stained highly positive for cathepsin X, showing a significant difference to the staining of normal prostate glands. In contrast, relatively weak and heterogeneous staining was observed for cathepsins F, B, and L. Up-regulation of cathepsin X at the protein level was confirmed by Western blotting. No statistically significant difference was observed at the mRNA level. PCR of genomic DNA revealed that cathepsin X up-regulation most likely occurs in the absence of genomic amplification.

CONCLUSIONS:

The high expression levels of cathepsin X both in PIN and invasive adenocarcinomas of the prostate suggest that cathepsin X may play a role in the early tumorigenesis of prostate cancer. Further studies are needed to define the utility of this cysteine protease as a diagnostic marker for the early detection of prostate cancer.

• Authors: Dorit K Nägler, Sabine Krüger, Angela Kellner, Edmund Ziomek, Robert Menard, Peter Buhtz, Matthias Krams, Albert Roessner, Udo Kellner
• Journal: The Prostate (Prostate) Vol. 60 Issue 2 Pg. 109-19 (Jul 01 2004) ISSN: 0270-4137 [Print] United States
• PMID: 15162377 (Publication Type: Journal Article)
• Copyright: Copyright 2004 Wiley-Liss, Inc.

Chemical References

• RNA, Messenger
• Cathepsins
• Cysteine Endopeptidases
• CTSK protein, human
• Cathepsin K

Topics

• Aged
• Aged, 80 and over
• Blotting, Western
• Cathepsin K
• Cathepsins (biosynthesis)
• Cysteine Endopeptidases (biosynthesis)
• Gene Expression Profiling
• Humans
• Immunohistochemistry
• In Situ Hybridization
• Male
• Middle Aged
• Prostatectomy
• Prostatic Intraepithelial Neoplasia (genetics, pathology)
• Prostatic Neoplasms (genetics, pathology)
• RNA, Messenger
• Reverse Transcriptase Polymerase Chain Reaction
• Up-Regulation