Expression of nuclear Notch3 in pancreatic adenocarcinomas is associated with adverse clinical features, and correlates with the expression of STAT3 and phosphorylated akt
Expression of nuclear Notch3 in pancreatic adenocarcinomas is associated with adverse clinical features, and correlates with the expression of STAT3 and phosphorylated akt
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DOI：
10.1002/jso.20894
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发表时间：
2008-01-01
影响因子：
2.5
通讯作者：
Manson, Margaret M.
中科院分区：
文献类型：
--
作者：
Doucas, Helena;Mann, Christopher D.;Manson, Margaret M.
背景和目的：Notch信号通路的重新激活发生在一系列人类恶性肿瘤中。先前的研究表明，Notch3在胰腺癌中表达，但既没有细胞定位，也没有与临床参数的关联已被描述。Notch3、临床终点和其他可能与Notch.Methods相互作用的蛋白质之间的关系因此被检查：对人胰腺癌（n = 23）和正常胰腺（n = 12）进行免疫组织化学研究，以评估Notch3、细胞周期蛋白D1、pAkt、STAT3和pSTAT3的表达。结果：Notch3在73.9%的肿瘤细胞质中明显过表达。在正常胰腺导管组织中未观察到核表达，但在43.5%的肿瘤中观察到。没有表达核Notch3的肿瘤是可切除的。Notch3与STAT3、pSTAT3和pAkt的表达和细胞内定位之间存在显著相关性，但与cyclin D1无关。结论：Notch3在肿瘤细胞核中的存在可能代表了Notch3蛋白的功能激活，并与更具有侵袭性的肿瘤表型明显相关。与STAT3，pSTAT3和pAkt表达的相关性以前没有被描述过，这些蛋白质的同时细胞内定位表明它们之间的功能关系。
Background and Objectives: Reactivation of the Notch signalling pathway occurs in a range of human malignancies. Previous research suggests that Notch3 is expressed in pancreatic adenocarcinomas, but neither cellular location nor association with clinical parameters has been described. The relationship between Notch3, clinical endpoints, and other proteins with potential to interact with Notch was therefore examined.Methods: An immunohistochemical study was performed on human pancreatic adenocarcinoma (n = 23) and normal pancreas (n = 12), to assess expression of Notch3, cyclin D1, pAkt, STAT3 and pSTAT3. Inummohistochemical data were then correlated with clinicopathological characteristics.Results: Notch3 was significantly overexpressed in the cytoplasm of 73.9% of tumours. Nuclear expression was not observed in normal pancreatic ductal tissue, but was noted in 43.5% of tumours. No tumour expressing nuclear Notch3 was resectable. There were significant correlations between expression and intracellular location of Notch3 and each of STAT3, pSTAT3 and pAkt, but not cyclin D1.Conclusion: The presence of Notch3 in tumour nuclei is likely to represent functional activation of the protein, and is clearly linked to a more aggressive tumour phenotype. The correlation with STAT3, pSTAT3 and pAkt expression has not previously been described and the concurrent intracellular localisation of these proteins suggests a functional relationship between them.