Up-regulation of cathepsin X in prostate cancer and prostatic intraepithelial neoplasia
Up-regulation of cathepsin X in prostate cancer and prostatic intraepithelial neoplasia
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DOI：
10.1002/pros.20046
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发表时间：
2004-07-01
期刊：
影响因子：
2.8
通讯作者：
Kellner, U
中科院分区：
文献类型：
--
作者：
Nägler, DK;Krüger, S;Kellner, U
背景。越来越多的证据表明，几种蛋白酶与前列腺癌的进展有关。在前列腺癌中经常扩增的位点是染色体区域20q13。有趣的是，其中一个编码半胱氨酸蛋白酶组织蛋白酶X的基因映射到这个区域。本研究的目的是评估组织蛋白酶X在恶性和非恶性前列腺组织样本中的表达模式。从56例根治性前列腺切除术后的男性中获得了匹配的恶性和非恶性组织标本。采用Western blotting、免疫组织化学、定量RT-PCR和原位杂交等多种检测方法对组织蛋白酶X进行蛋白和mRNA水平的定量检测。此外，用PCR方法对基因组DNA进行分析，寻找可能扩增的基因。对前列腺根治标本经福尔马林固定、石蜡包埋的切片进行免疫组化分析，使用抗人原athepsin X的多克隆抗体，发现正常前列腺腺泡基底细胞染色。前列腺上皮内瘤样增生（PINs）和前列腺癌组织蛋白酶X染色呈高阳性，与正常前列腺染色有显著差异。相反，组织蛋白酶F、B和l的染色相对较弱且呈异质染色。Western blotting证实组织蛋白酶X在蛋白水平上表达上调。mRNA水平差异无统计学意义。基因组DNA PCR结果显示，组织蛋白酶X的上调很可能发生在没有基因组扩增的情况下。组织蛋白酶X在PIN和前列腺浸润性腺癌中的高表达表明，组织蛋白酶X可能在前列腺癌的早期肿瘤发生中发挥作用。需要进一步的研究来确定这种半胱氨酸蛋白酶作为前列腺癌早期检测的诊断标志物的效用。中华医学会医学分会，2004。(C) 2004 Wiley-Liss, Inc。
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 heterogenous staining was observed for cathepsins F, B, and L. Upregulation 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. Prostate 60: 109-119, 2004. (C) 2004 Wiley-Liss, Inc.