Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
Pathobiology. 2013;80(2):60-9. doi: 10.1159/000341396. Epub 2012 Aug 29.
Genes expressed only in cancer tissue or specific organs will be useful molecular markers. To identify genes that encode secreted proteins present in prostate cancer (PCa), we generated Escherichia coli ampicillin secretion trap (CAST) libraries from PCa and normal prostate (NP).
We identified 15 candidate genes that encode secreted proteins present in PCa and NP. Quantitative RT-PCR analysis revealed that MSMB, NBL1 and AZGP1 were expressed with much higher specificity in PCa and NP than in 14 other kinds of normal tissue. We focused on NBL1, which was originally identified as a putative tumor suppressor gene. Western blot analysis revealed that NBL1 protein was highly expressed in both cell lysate and culture media of the DU145 PCa cell line. Immunohistochemical analysis showed that NBL1 expression was highly detected in and restricted to NP and PCa and was significantly down-regulated in PCa. NBL1 expression was significantly reduced according to the tumor stage, Gleason grade and preoperative prostate-specific antigen (PSA) value.
NBL1 is a secreted protein that is highly restricted to the prostate. Underexpression of NBL1 correlated with PCa progression. NBL1 might be a candidate tumor marker for PCa in addition to PSA.
仅在肿瘤组织或特定器官中表达的基因将成为有用的分子标志物。为了鉴定存在于前列腺癌（PCa）中的编码分泌蛋白的基因，我们从 PCa 和正常前列腺（NP）中生成了大肠杆菌氨苄青霉素分泌陷阱（CAST）文库。
我们鉴定出 15 个候选基因，这些基因编码存在于 PCa 和 NP 中的分泌蛋白。定量 RT-PCR 分析显示，MSMB、NBL1 和 AZGP1 在 PCa 和 NP 中的表达特异性明显高于其他 14 种正常组织。我们专注于 NBL1，它最初被鉴定为一种潜在的肿瘤抑制基因。Western blot 分析显示，NBL1 蛋白在 DU145 PCa 细胞系的细胞裂解物和培养物中均高度表达。免疫组织化学分析显示，NBL1 表达在 NP 和 PCa 中高度检测到，并且仅限于 NP 和 PCa，在 PCa 中显著下调。NBL1 的表达根据肿瘤分期、Gleason 分级和术前前列腺特异性抗原（PSA）值显著降低。
NBL1 是一种高度限制在前列腺中的分泌蛋白。NBL1 的低表达与 PCa 的进展相关。NBL1 可能是 PSA 之外 PCa 的候选肿瘤标志物。
