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

DOIResolve DOI: http://doi.org/10.1002/pros.20046
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Pages109119; # of pages: 11
SubjectAdenocarcinoma; analysis; Cathepsins; Cysteine; Dna; Genes; Human; Immunohistochemistry; In Situ Hybridization; methods; pha; Up-Regulation
AbstractBACKGROUND: 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 heterogenous 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. Copyright 2004 Wiley-Liss, Inc
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AffiliationNRC Biotechnology Research Institute; National Research Council Canada
Peer reviewedNo
NRC number46209
NPARC number3538821
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Record identifier0d27145c-0b8a-4e81-a8d4-7ba7e5f4fd95
Record created2009-03-01
Record modified2016-05-09
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