Reich Reuven, Hadar Shany, Davidson Ben
Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel; E-Mail:
Int J Mol Sci. 2011 Feb 11;12(2):1133-45. doi: 10.3390/ijms12021133.
The present study analyzed the expression and clinical role of the protein of regenerating liver (PRL) phosphatase family in ovarian carcinoma. PRL1-3 mRNA expression was studied in 184 tumors (100 effusions, 57 primary carcinomas, 27 solid metastases) using RT-PCR. PRL-3 protein expression was analyzed in 157 tumors by Western blotting. PRL-1 mRNA levels were significantly higher in effusions compared to solid tumors (p < 0.001), and both PRL-1 and PRL-2 were overexpressed in pleural compared to peritoneal effusions (p = 0.001). PRL-3 protein expression was significantly higher in primary diagnosis pre-chemotherapy compared to post-chemotherapy disease recurrence effusions (p = 0.003). PRL-1 mRNA expression in effusions correlated with longer overall survival (p = 0.032), and higher levels of both PRL-1 and PRL-2 mRNA correlated with longer overall survival for patients with pre-chemotherapy effusions (p = 0.022 and p = 0.02, respectively). Analysis of the effect of laminin on PRL-3 expression in ovarian carcinoma cells in vitro showed dose-dependent PRL-3 expression in response to exogenous laminin, mediated by Phospholipase D. In contrast to previous studies associating PRL-3 with poor outcome, our data show that PRL-3 expression has no clinical role in ovarian carcinoma, whereas PRL-1 and PRL-2 expression is associated with longer survival, suggesting that PRL phosphatases may be markers of improved outcome in this cancer.
本研究分析了再生肝蛋白（PRL）磷酸酶家族在卵巢癌中的表达及临床作用。采用逆转录聚合酶链反应（RT-PCR）研究了184例肿瘤（100例积液、57例原发性癌、27例实性转移瘤）中PRL1 - 3 mRNA的表达。通过蛋白质免疫印迹法分析了157例肿瘤中PRL-3蛋白的表达。与实性肿瘤相比，积液中PRL-1 mRNA水平显著更高（p < 0.001），与腹腔积液相比，PRL-1和PRL-2在胸腔积液中均过表达（p = 0.001）。与化疗后疾病复发积液相比，化疗前初诊时PRL-3蛋白表达显著更高（p = 0.003）。积液中PRL-1 mRNA表达与总生存期延长相关（p = 0.032），化疗前积液患者中PRL-1和PRL-2 mRNA水平较高均与总生存期延长相关（分别为p = 0.022和p = 0.02）。体外分析层粘连蛋白对卵巢癌细胞中PRL-3表达的影响显示，外源性层粘连蛋白介导的PRL-3表达呈剂量依赖性，由磷脂酶D介导。与之前将PRL-3与不良预后相关联的研究不同，我们的数据表明PRL-3表达在卵巢癌中无临床作用，而PRL-1和PRL-2表达与更长生存期相关，提示PRL磷酸酶可能是该癌症预后改善的标志物。
