The Search for Secreted Proteins in Prostate Cancer by the Escherichia coli Ampicillin Secretion Trap: Expression of NBL1 Is Highly Restricted to the Prostate and Is Related to Cancer Progression
The Search for Secreted Proteins in Prostate Cancer by the Escherichia coli Ampicillin Secretion Trap: Expression of NBL1 Is Highly Restricted to the Prostate and Is Related to Cancer Progression
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DOI：
10.1159/000341396
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发表时间：
2012-08
期刊：
影响因子：
5
通讯作者：
Tetsutaro Hayashi;K. Sentani;N. Oue;S. Ohara;J. Teishima;Katsuhiro Anami;N. Sakamoto;A. Matsubara;W. Yasui
中科院分区：
文献类型：
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作者：
Tetsutaro Hayashi;K. Sentani;N. Oue;S. Ohara;J. Teishima;Katsuhiro Anami;N. Sakamoto;A. Matsubara;W. Yasui
目的：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记。为了鉴定前列腺癌（PCa）中存在的编码分泌蛋白的基因，我们从前列腺癌和正常前列腺（NP）中生成了大肠杆菌氨青霉素分泌陷阱（CAST）文库。方法和结果：我们鉴定了15个候选基因，编码PCa和NP中存在的分泌蛋白。定量RT-PCR分析显示，MSMB、NBL1和AZGP1在PCa和NP中表达的特异性明显高于其他14种正常组织。我们关注的是NBL1，它最初被认为是一种推定的肿瘤抑制基因。Western blot分析显示，NBL1蛋白在DU145 PCa细胞株的细胞裂解液和培养基中均有高表达。免疫组化分析显示，NBL1在NP和PCa中高度表达且仅限于NP和PCa，在PCa中显著下调表达。根据肿瘤分期、Gleason分级及术前前列腺特异性抗原（PSA）值，NBL1的表达均显著降低。结论：NBL1是一种高度局限于前列腺的分泌蛋白。NBL1低表达与前列腺癌进展相关。除了PSA外，NBL1可能是PCa的候选肿瘤标志物。
Aims: 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). Methods and Results: 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. Conclusion: 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.