Analysis of β-catenin gene mutations in pancreatic tumors

Analysis of β-catenin gene mutations in pancreatic tumors
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DOI:
10.1159/000007704
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发表时间:
1999-11-01
期刊:
影响因子:
3.2
通讯作者:
Bartsch, D
Bartsch, D
中科院分区:
医学3区
文献类型:
--
作者:
Gerdes, B;Ramaswamy, A;Bartsch, D

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背景/目的:在胰腺癌中发现了腺瘤性息肉病(APC)抑癌基因的突变。APC基因调控β-连环蛋白-Tcf途径。这一途径的主要参与者是由β-连环蛋白基因编码的β-连环蛋白。各种不同的肿瘤,包括结肠癌、前列腺癌、子宫内膜癌和肝细胞癌,都带有β-连环蛋白基因外显子3的突变。本研究的目的是确定β-连环蛋白基因在胰腺外分泌和内分泌肿瘤发生中的作用。方法:采用单链构象多态分析和DNA测序技术检测78例导管胰腺癌、14例导管胰腺癌细胞株和33例胰腺内分泌肿瘤组织中β-catenin基因外显子3的突变情况。此外,通过免疫组织化学分析了40例导管胰腺癌细胞内β-连环素的积聚,表明β-连环素基因发生了变化。结果:111例胰腺外分泌和内分泌肿瘤及14株胰腺癌细胞均未检测到β-连环素基因外显子3的突变。在40例胰腺癌中,没有一例发现细胞内β-连环素积聚。结论:β-连环蛋白基因作为β-连环蛋白-Tcf通路的主要成员,在胰腺肿瘤的发生中不起重要作用。
Background/Aim: Mutations of the adenomatous polyposis coli (APC) tumor suppressor gene have been described in a subset of pancreatic carcinomas. The APC gene modulates the beta-catenin-Tcf pathway. The major player in this pathway is the beta-catenin protein encoded by the beta-catenin gene. A variety of different tumors, including colon, prostate, endometrial, and hepatocellular carcinomas, carry mutations in exon 3 of the beta-catenin gene. The aim of this study was to determine the role of the beta-catenin gene in the genesis of exocrine and endocrine tumors of the pancreas. Methods: 78 ductal pancreatic adenocarcinomas, 14 ductal pancreatic cancer cell lines, and 33 endocrine pancreatic tumors were evaluated for mutations in exon 3 of the beta-catenin gene by single-strand conformation polymorphism analysis and direct DNA sequencing. in addition, 40 ductal pancreatic adenocarcinomas were analyzed for intracellular beta-catenin accumulation by immunohistochemistry, indicating alterations of the beta-catenin gene. Results: Neither the 111 exocrine and endocrine pancreatic tumors nor the 14 pancreatic cancer cell lines carried mutations in exon 3 of the beta-catenin gene. Intracellular beta-catenin accumulation was not identified in any of the 40 pancreatic adenocarcinomas. Conclusion: These data suggest that the beta-catenin gene as the major player of the beta-catenin-Tcf pathway does not play an important role in the genesis of pancreatic tumors.