Dysregulation of β-catenin expression correlates with tumor differentiation in pancreatic duct adenocarcinoma
Dysregulation of β-catenin expression correlates with tumor differentiation in pancreatic duct adenocarcinoma
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DOI：
10.1245/aso.2003.05.003
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发表时间：
2003-04-01
影响因子：
3.7
通讯作者：
Groden, J
中科院分区：
文献类型：
--
作者：
Lowy, AM;Fenoglio-Preiser, C;Groden, J
背景：β-连环蛋白作为E-钙粘蛋白/连环蛋白粘附复合物的一个组成部分，维持上皮细胞的完整性。β-连环蛋白也作为Wnt信号转导途径的一部分发挥作用，通过与Tcf/Lef转录因子的相互作用将促生长信号传递到细胞核。以前的报告已经证明了改变β-连环蛋白的表达在许多肿瘤类型，但是，关于β-连环蛋白的表达在胰腺癌的报告一直conflicted.Methods：β-连环蛋白的表达进行了检查，在10个胰腺癌细胞系的Western和北方分析和免疫荧光。结果：10株胰腺癌细胞系中有4株β-catenin表达降低。在32例胰腺癌（56%）中观察到膜表达减少，并与肿瘤分化丧失相关。在两个肿瘤（4%）中发现了细胞核β-连环蛋白表达。β-连环蛋白表达存在于所有7个病灶的原位癌，然而，核表达是主要的7 cases.Conclusions：β-连环蛋白表达的改变是常见的胰腺癌，然而，信号和粘附功能可能会在不同的时间在肿瘤进展过程中受到干扰。因此，β-连环蛋白的失调可能通过不同的机制促进这种疾病的发展和进展。
Background: beta-Catenin functions as an integral part of the E-cadherin/catenin adhesion complex to maintain epithelial cell integrity. beta-Catenin also functions as part of the Wnt signal transduction pathway to transmit growth-promoting signals to the nucleus via its interactions with Tcf/Lef transcription factors. Previous reports have demonstrated altered beta-catenin expression in numerous tumor types; however, reports regarding beta-catenin expression in pancreatic cancer have been conflicting.Methods: beta-Catenin expression was examined in 10 pancreatic cancer cell lines by Western and Northern analysis and by immunofluorescence. Expression was also examined by immunohistochemistry in 57 primary pancreatic cancers and 7 foci of carcinoma-in-situ.Results: Reduced expression of beta-catenin was observed in 4 of 10 pancreatic cancer cell lines. Reduced membranous expression was noted in 32 pancreatic cancers (56%) and correlated with loss of tumor differentiation. Nuclear beta-catenin expression was identified in two tumors (4%). beta-Catenin expression was present in all seven foci of carcinoma-in-situ; however, nuclear expression was predominant in four of the seven cases.Conclusions: Alterations in beta-catenin expression are common in pancreatic cancer; however, signaling and adhesion functions may be perturbed at different times during tumor progression. Therefore, dysregulation of beta-catenin may contribute to the development and progression of this disease through distinct mechanisms.