Institute for Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
Prostate. 2012 Nov;72(15):1678-87. doi: 10.1002/pros.22521. Epub 2012 Apr 2.
We recently established the rationale that NRBP1 (nuclear receptor binding protein 1) has a potential growth-promoting role in cell biology. NRBP1 interacts directly with TSC-22, a potential tumor suppressor gene that is differently expressed in prostate cancer. Consequently, we analyzed the role of NRBP1 expression in prostate cancer cell lines and its expression on prostate cancer tissue microarrays (TMA).
The effect of NRBP1 expression on tumor cell growth was analyzed by using RNAi. NRBP1 protein expression was evaluated on two TMAs containing prostate samples from more than 1,000 patients. Associations with clinico-pathological features, the proliferation marker Ki67 and survival data were analyzed.
RNAi mediated silencing of NRBP1 expression in prostate cancer cell lines resulted in reduced cell growth (P < 0.05). TMA analysis revealed NRBP1 protein expression in benign prostate hyperplasia in 6% as compared to 60% in both, high-grade intraepithelial neoplasia and prostate cancer samples. Strong NRBP1 protein expression was restricted to prostate cancer and correlated with higher expression of the proliferation marker Ki67 (P < 0.05). Further, patients with strong NRBP1 protein expression showed poor clinical outcomes (P < 0.05). Analysis of matched localized cancer tissues before and after castration revealed that post-therapy-related repression of NRBP1 expression was significantly associated with better overall survival.
We demonstrate that expression of NRBP1 is up-regulated during the progression of prostate cancer and that high NRBP1 expression is linked with poor prognosis and enhanced tumor cell growth.
我们最近提出了一个理论，即 NRBP1（核受体结合蛋白 1）在细胞生物学中具有潜在的促进生长作用。NRBP1 与 TSC-22 直接相互作用，TSC-22 是一种潜在的肿瘤抑制基因，在前列腺癌中表达不同。因此，我们分析了 NRBP1 表达在前列腺癌细胞系中的作用及其在前列腺癌组织微阵列（TMA）上的表达。
通过使用 RNAi 分析 NRBP1 表达对肿瘤细胞生长的影响。在包含来自 1000 多个患者的前列腺样本的两个 TMA 上评估 NRBP1 蛋白表达。分析与临床病理特征、增殖标志物 Ki67 和生存数据的关联。
在前列腺癌细胞系中，RNAi 介导的 NRBP1 表达沉默导致细胞生长减少（P<0.05）。TMA 分析显示，良性前列腺增生中的 NRBP1 蛋白表达为 6%，而高级别上皮内瘤变和前列腺癌样本中的 NRBP1 蛋白表达则为 60%。NRBP1 蛋白表达强烈限于前列腺癌，并与增殖标志物 Ki67 的高表达相关（P<0.05）。此外，NRBP1 蛋白表达强烈的患者临床结局较差（P<0.05）。分析配对的局部癌症组织在去势前后的表达情况，发现治疗后 NRBP1 表达的抑制与总生存的改善显著相关。
我们证明了 NRBP1 的表达在前列腺癌的进展过程中上调，并且高 NRBP1 表达与不良预后和增强的肿瘤细胞生长相关。
