Reduced expression of PTEN and increased PTEN phosphorylation at residue Ser380 in gastric cancer tissues: A novel mechanism of PTEN inactivation
Reduced expression of PTEN and increased PTEN phosphorylation at residue Ser380 in gastric cancer tissues: A novel mechanism of PTEN inactivation
复制标题
胃癌组织中PTEN表达减少和PTEN残基Ser380磷酸化增加：PTEN失活的新机制
DOI：
10.1016/j.clinre.2012.03.002
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发表时间：
2013-02-01
影响因子：
2.7
通讯作者：
Lu, Nong-Hua
中科院分区：
文献类型：
--
作者：
Yang, Zhen;Yuan, Xiao-Gang;Lu, Nong-Hua
目的：PTEN是不同肿瘤的抑癌基因。本研究旨在测定不同胃组织组织学标本中PTEN蛋白表达及PTEN残基380位点磷酸化水平（p-PTEN）。方法：选取正常胃黏膜、慢性胃炎、肠化生、非典型增生、胃癌组织标本179例，进行PTEN及p-PTEN表达的免疫组化分析。采用Western blot法检测4株胃癌AGS、MKN-45、MKN-28、SGC-7901细胞株和1株非胃癌GES-1细胞株PTEN和p-PTEN蛋白的表达。结果：PTEN蛋白在胃癌组织中的表达水平与正常胃黏膜、慢性胃炎、肠化生和非典型增生相比均显著降低（P < 0.05）。与正常胃黏膜组织和慢性胃炎组织相比，肠化生组织、非典型增生组织和胃癌组织中P - pten蛋白水平显著升高（P < 0.05）。然而，PTEN和p-PTEN的表达与胃癌患者的临床病理特征没有相关性。胃癌细胞系中p-PTEN和PTEN的比值高于非恶性细胞。结论：本研究表明PTEN和p-PTEN在Ser380位点的异常表达是胃癌发生的早期事件，PTEN在Ser380位点的磷酸化可能是PTEN失活的机制之一。(C) 2012 Elsevier Masson SAS。版权所有。
Aim: PTEN is a tumor suppressor gene in different cancers. This study was to determine the protein expression of PTEN and phosphorylation of PTEN (p-PTEN) at residue Ser380 in different histology specimens of gastric tissues.Methods: A total of 179 tissue specimens of normal gastric mucosa, chronic gastritis, intestinal metaplasia, dysplasia, and gastric cancer were recruited for immunohistochemical analysis of PTEN and p-PTEN expression. Four gastric cancer AGS, MKN-45, MKN-28, and SGC-7901 cell lines and a non-cancerous gastric GES-1 cell line were used to detect expression of PTEN and p-PTEN protein using Western blot.Results: Expression level of PTEN protein was significantly decreased in gastric cancer tissues compared to normal gastric mucosa, chronic gastritis, intestinal metaplasia and dysplasia (P < 0.05). In contrast, p-PTEN protein level was significantly increased in intestinal metaplasia, dysplasia and gastric cancer compared to normal gastric mucosa and chronic gastritis (P < 0.05). However, there was no any association of PTEN and p-PTEN expression with clinicopathological characteristics from gastric cancer patients. Moreover, the ratio of p-PTEN and PTEN was higher in gastric cancer cell lines than that of the non-malignant cells.Conclusions: This study demonstrated that aberrant expression of PTEN and p-PTEN at residue Ser380 was early event that could contribute to gastric carcinogenesis, and that PTEN phosphorylation at residue Ser380 could be a mechanism for PTEN inactivation. (C) 2012 Elsevier Masson SAS. All rights reserved.