Zhou Jiahua, Feng Yongjiang, Tao Ketao, Su Zhanhai, Yu Xiaojin, Zheng Jie, Zhang Lihua, Yang Detong
Department of General Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, P.R. China.
Basic Medical Research Center, Qinghai University, Xining 810001, P.R. China.
Int J Oncol. 2014 Jun;44(6):2059-67. doi: 10.3892/ijo.2014.2381. Epub 2014 Apr 10.
Pancreatic carcinoma is the most common pancreatic malignancy and is associated with a very poor prognosis. Therefore, new prognostic factors and new treatment strategies are clearly needed. In this study, we retrospectively studied the levels of phosphorylated ezrin in 19 patients with pancreatic carcinoma by immunohistochemical analysis and determined the correlation between protein expression, clinicopathological characteristics and prognosis in pancreatic adenocarcinoma. We also characterized the phenotype of the overexpression of wild-type and phosphorylated ezrin and merlin in human pancreatic cancer cell lines. A significant correlation between the levels of phosphorylated ezrin 353 and ezrin 567 and the stage of pancreatic cancer was observed. Moreover, Kaplan-Meier analysis revealed that patients with high levels of phosphorylated ezrin had a significantly poorer survival rate (P<0.05). In addition, the overexpression of wild-type merlin or ezrin inhibited cell proliferation, migration and adhesion. However, the overexpression of T567D ezrin, a mutant that mimics permanent phosphorylation, promoted the proliferation, adhesion and migration of the pancreatic adenocarcinoma cell line SW1990. The overexpression of S518D merlin inhibited the growth of SW1990 and did not affect migration or adhesion. These results suggest that the phosphorylation of ezrin may contribute to the progression of pancreatic carcinoma and that the level of phosphorylated ezrin may serve as an adverse prognostic factor for pancreatic carcinoma.
胰腺癌是最常见的胰腺恶性肿瘤，预后很差。因此，显然需要新的预后因素和新的治疗策略。在本研究中，我们通过免疫组织化学分析回顾性研究了19例胰腺癌患者中磷酸化埃兹蛋白的水平，并确定了胰腺腺癌中蛋白表达、临床病理特征与预后之间的相关性。我们还对人胰腺癌细胞系中野生型和磷酸化埃兹蛋白及墨林过表达的表型进行了表征。观察到磷酸化埃兹蛋白353和埃兹蛋白567的水平与胰腺癌分期之间存在显著相关性。此外，Kaplan-Meier分析显示，磷酸化埃兹蛋白水平高的患者生存率显著较低（P<0.05）。此外，野生型墨林或埃兹蛋白的过表达抑制细胞增殖、迁移和黏附。然而，模拟永久磷酸化的突变体T567D埃兹蛋白的过表达促进了胰腺腺癌细胞系SW1990的增殖、黏附和迁移。S518D墨林的过表达抑制了SW1990的生长，且不影响迁移或黏附。这些结果表明，埃兹蛋白的磷酸化可能促进胰腺癌的进展，且磷酸化埃兹蛋白水平可能作为胰腺癌的不良预后因素。
