Cyclin D1 overexpression in thyroid tumours from a radio-contaminated area and its correlation with Pin1 and aberrant β-catenin expression
Cyclin D1 overexpression in thyroid tumours from a radio-contaminated area and its correlation with Pin1 and aberrant β-catenin expression
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DOI：
10.1002/path.1534
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发表时间：
2004-04-01
影响因子：
7.3
通讯作者：
Sekine, I
中科院分区：
文献类型：
--
作者：
Nakashima, M;Meirmanov, S;Sekine, I
细胞周期蛋白D1是Wnt信号传导中异常β-连环蛋白转录激活的靶分子，而脯氨酰异构酶Pin 1直接或通过β-连环蛋白在癌细胞中的积累促进细胞周期蛋白D1过表达。本研究旨在通过检测14例甲状腺滤泡性腺瘤（FAa）和14例甲状腺乳头状癌（PTC）来阐明Pin 1是否参与了甲状腺肿瘤发生中细胞周期蛋白D1的过度表达和β-连环蛋白的异常表达。免疫组化显示所有PTC细胞周期蛋白D1过表达和强胞浆β-连环蛋白和/或膜β-连环蛋白表达减少。TaqMan实时荧光定量PCR检测结果显示，45.5%的FAs和54.5%的PTC中存在cyclin D1 mRNA的过表达。免疫组化染色观察到PTC中Pinl的表达，并通过逆转录-PCR证实。在甲状腺肿瘤中，细胞周期蛋白D1和Pin 1/细胞质/细胞膜β-连环蛋白表达之间有很强的相关性（p < 0.001），Pin 1和细胞质（p < 0.001）/细胞膜（p = 0.002）β-连环蛋白表达之间也有很强的相关性。在PTC中未检测到fl-catenin基因突变。Western印迹分析表明，在具有野生型β-连环蛋白和APC基因的人PTC细胞系中，细胞周期蛋白D1和β-连环蛋白以及Pin 1表达水平较高。这项研究表明，细胞周期蛋白D1的过度表达和异常β-连环蛋白的表达在甲状腺肿瘤的意义。Pin 1的表达似乎与甲状腺肿瘤如FA和PTC中细胞周期蛋白D1的水平和异常β-连环蛋白表达密切相关。Pinl可能是甲状腺癌发生过程中调控cyclin D1和beta-catenin表达的重要因子。版权所有（C）2004大不列颠和爱尔兰病理学会。出版社：John Wiley Sons，Ltd
Cyclin D1 is a target molecule transcriptionally activated by aberrant beta-catenin in Wnt signalling, while prolyl isomerase Pin1 promotes cyclin D1 overexpression directly or through accumulation of beta-catenin in cancer cells. This study aimed to elucidate whether Pin1 was involved in cyclin D1 overexpression and aberrant beta-catenin in thyroid tumourigenesis by examining 14 follicular adenomas (FAa) and 14 papillary thyroid carcinomas (PTCs). All PTCs displayed cyclin D1 overexpression and strong cytoplasmic beta-catenin and/or decreased membrane beta-catenin expression by immunohistochemistry. Overexpression of cyclin D1 mRNA was observed in 45.5% of FAs and 54.5% of PTCs by TaqMan real-time PCR. Pinl expression was observed in PTC by immunostaining and was confirmed by reverse transcriptase-PCR. There was a strong correlation between cyclin D1 and Pin1/cytoplasmic/membrane beta-catenin expression (p < 0.001), and between Pinl and cytoplasmic (p < 0.001)/membrane (p = 0.002) beta-catenin expression in thyroid tumours. Mutation of the fl-catenin gene could not be detected in PTC. Western blot analysis demonstrated high levels of cyclin D1 and beta-catenin as well as Pin1 expression in a human PTC cell line possessing wild-type beta-catenin and APC genes. This study suggests that both cyclin D1 overexpression and aberrant beta-catenin expression are of significance in thyroid tumours. Pin1 expression appears to correlate closely with the level of cyclin D1 and aberrant beta-catenin expression in thyroid tumours such as FA and PTC. Pinl may be an important factor in regulating cyclin D1 and beta-catenin expression during thyroid carcinogenesis. Copyright (C) 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley Sons, Ltd.