Characterization of KLK4 expression and detection of KLK4-specific antibody in prostate cancer patient sera
Characterization of KLK4 expression and detection of KLK4-specific antibody in prostate cancer patient sera
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DOI：
10.1038/sj.onc.1205786
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发表时间：
2002-10-10
期刊：
影响因子：
8
通讯作者：
Watanabe, Y
中科院分区：
文献类型：
--
作者：
Day, CH;Fanger, GR;Watanabe, Y
鉴别高水平表达的前列腺肿瘤或前列腺组织特异性基因并利用其蛋白产物作为靶标的能力将极大地有助于前列腺癌的诊断和治疗。利用基于聚合酶链反应（PCR）的减法技术，我们从人前列腺cDNA中恢复了最近描述的KLK4（前列腺酶）基因。本研究利用cDNA定量PCR和免疫组织化学进一步分析了KLK4基因在人前列腺肿瘤中的表达，证实该基因在正常人前列腺组织、原发性和转移性前列腺肿瘤样本中均以mRNA和蛋白水平特异性表达。定量mRNA分析也显示肾上腺、唾液腺和甲状腺低水平表达。最后，研究证明前列腺癌患者血清中含有特异性结合重组KLK4蛋白的抗体。该抗体已在表位定位实验中用于检测klk4特异性肽。肿瘤和正常前列腺组织中KLK4 mRNA和蛋白的相对特异性表达谱和升高水平，以及癌症患者血清中可检测到的KLK4特异性抗体，支持了确定KLK4是否可以在前列腺癌的诊断、残留疾病的监测或作为免疫治疗靶点方面发挥作用的额外努力。
The ability to identify prostate tumor or prostate tissue specific genes that are expressed at high levels and use their protein products as targets could greatly aid in the diagnosis and treatment of prostate cancer. Using a polymerase chain reaction (PCR)-based subtraction technique, we have recovered the recently described KLK4 (prostase) gene from human prostate cDNA. In this study, KLK4 gene expression in human prostate tumors was further characterized using cDNA quantitative PCR and immunohistochemistry, demonstrating that the gene is specifically expressed at both the mRNA and protein levels in normal human prostate tissue, and in both primary and metastatic prostate tumor samples. Quantitative mRNA analysis also demonstrated low level expression including adrenal gland, salivary gland and thyroid. Finally, it was demonstrated that prostate cancer patient sera contain antibodies that bind specifically to recombinant KLK4 protein. This antibody has been used to detect KLK4-specific peptides in epitope mapping experiments. The relatively specific expression profile and elevated level of KLK4 mRNA and protein in both tumor and normal prostate tissues, in addition to detectable KLK4-specific antibody in cancer patient sera, supports additional efforts to determine if KLK4 can play a role in the diagnosis of prostate cancer, the monitoring of residual disease, or act as a target for immunotherapy.