Overexpression of PrPc and its antiapoptosis function in gastric cancer
Overexpression of PrPc and its antiapoptosis function in gastric cancer
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DOI：
10.1159/000092488
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发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
Fan, DM
中科院分区：
文献类型：
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作者：
Liang, J;Pan, YL;Fan, DM
PrPc是本实验室发现的一种糖基磷脂酰肌醇锚定的膜蛋白，在胃癌细胞系中广泛表达。为探讨其在人胃癌组织中的生物学意义，我们用抗3F4单抗进行免疫组织化学染色，对124例人胃癌组织标本进行了检测。与正常组织相比，胃腺癌中PrPC表达增强，且与组织分化程度(WHO和Lauren分类)和肿瘤进展(pTNM分期)有关。为了更好地了解其潜在的机制，我们将PrPc和两对RNAi导入低分化胃癌细胞系AGS，发现PrPC抑制ROS并减缓细胞的凋亡。进一步的研究证明，在PrPC转基因细胞中，凋亡相关蛋白Bcl2表达上调，而P53和Bax表达下调。在PrPc siRNA转基因细胞中观察到了相反的效应。这些结果有力地提示PrPc可能通过依赖于Bcl2的凋亡途径在胃癌细胞中作为有效的抗凋亡蛋白发挥作用。进一步研究这些关系的机制可能会丰富PrP的知识，更好地理解胃癌的本质，并进一步开发可能的阻断或逆转胃癌发展的策略。版权所有(C)2006 S.Karger AG，巴塞尔。
Cellular prion protein (PrPc), a glycosylphosphaticlylinositol-anchored membrane protein, was found in our lab to be widely expressed in gastric cancer cell lines. In order to evaluate its biological significance in human gastric cancer, we investigated its expression in a large series of gastric tissue samples (n = 124) by immunohistochemical staining with the monoclonal antibody 3F4. Compared with normal tissues, gastric adenocarcinoma showed increased PrPC expression, correlated with the histopathological differentiation (according to the WHO and Lauren classifications) and tumor progression (as documented by pTNM staging). To better understand the underlying mechanism, we introduced the PrPc and two pairs of RNAi into the poorly differentiated gastric cancer cell line AGS and found that PrPC suppressed ROS and slowed down apoptosis in transfected cells. Further study proved that the apoptosis-related protein Bcl-2 was upregulated whereas p53 and Bax were downregulated in the PrPC-transfected cells. A reverse effect was observed in PrPc siRNA-transfected cells. These results strongly suggested that PrPc might play a role as an effective antiapoptotic protein through Bcl-2-dependent apoptotic pathways in gastric cancer cells. Further study into the mechanism of these relationships might enrich the knowledge of PrP, better our understanding of the nature of gastric carcinoma, and further develop possible strategies to block or reverse the development of gastric carcinoma. Copyright (c) 2006 S. Karger AG, Basel.