Up-regulation of cathepsin X in prostate cancer and prostatic intraepithelial neoplasia.
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.
Nägler
Dorit K
DK
Department of Clinical Chemistry and Clinical Biochemistry, University Hospital of Surgery-City, Ludwig-Maximilians-University, Munich, Germany. dorit.naegler@clinbio.med.uni-muenchen.de
Krüger
Sabine
S
Kellner
Angela
A
Ziomek
Edmund
E
Menard
Robert
R
Buhtz
Peter
P
Krams
Matthias
M
Roessner
Albert
A
Kellner
Udo
U
D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D056657:Cathepsin K; D002403:Cathepsins / Q000096:biosynthesis*; D003546:Cysteine Endopeptidases / Q000096:biosynthesis; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D011468:Prostatectomy; D019048:Prostatic Intraepithelial Neoplasia / Q000235:genetics* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D012333:RNA, Messenger; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534130:CTSK protein, human; D056657:Cathepsin K