The role of epithelial mesenchymal transition markers in thyroid carcinoma progression.
The role of epithelial mesenchymal transition markers in thyroid carcinoma progression.
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DOI：
10.1007/s12022-013-9272-9
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发表时间：
2013-12
影响因子：
4.4
通讯作者：
Lloyd RV
中科院分区：
文献类型：
--
作者：
Montemayor-Garcia C;Hardin H;Guo Z;Larrain C;Buehler D;Asioli S;Chen H;Lloyd RV
了解甲状腺癌进展的分子机制可能为更有效地治疗侵袭性甲状腺癌提供靶点。上皮-间充质转化(EMT)是肿瘤进展的主要病理机制，与癌细胞获得干细胞性有关。我们用组织芯片(TMA)检测了E-cadherin启动子中与E-box元件结合激活EMT的ZEB1基因的表达，以及E-cadherin在正常和肿瘤性甲状腺组织中的表达。甲状腺滤泡性腺瘤(FA，n=32)、滤泡性甲状腺癌(FTC，n=28)和乳头状癌(PTC，n=57)均表达E-钙粘素，而大多数间变性甲状腺癌(ATC，n=10)E-钙粘素阴性，ZEB1阳性。对10个完整的ATC切片的验证集显示，90%的病例ZEB1阳性，所有病例E-钙粘素均为阴性。对三种细胞系(正常甲状腺、NTHY-或13-1、PTC、TPC-1和ATC、THJ-21T)的分析表明，ATC细胞表达最高水平的ZEB1，而正常甲状腺细胞表达最高水平的E-钙粘附素。定量RT-PCR分析显示，ATC组Smad7mRNA的表达明显高于其他组(p<；0.05)。这些结果表明，与分化较好的甲状腺癌相比，甲状腺癌中E-钙粘蛋白表达降低，ZEB1表达增加，Smad7的表达增加可能与甲状腺肿瘤的进展有关。
Understanding the molecular mechanisms involved in thyroid cancer progression may provide targets for more effective treatment of aggressive thyroid cancers. Epithelial-mesenchymal transition (EMT) is a major pathologic mechanism in tumor progression and is linked to the acquisition of stem-like properties of cancer cells. We examined expression of ZEB1 which activates EMT by binding to the E-box elements in the E-cadherin promoter, and expression of E-cadherin in normal and neoplastic thyroid tissues in a tissue microarray (TMA) which included 127 neoplasms and 10 normal thyroid specimens. Thyroid follicular adenomas (FA, n=32), follicular thyroid carcinomas (FTC, n=28), and papillary thyroid carcinomas (PTC, n=57) all expressed E-cadherin and were mostly negative for ZEB1 while most anaplastic thyroid carcinomas (ATC, n=10) were negative for E-cadherin, but positive for ZEB1. A validation set of 10 whole sections of ATCs showed 90% of cases positive for ZEB1 and all cases were negative for E-cadherin. Analysis of three cell lines (normal thyroid, NTHY-OR13-1; PTC, TPC-1 and ATC, THJ-21T) showed that the ATC cell line expressed the highest levels of ZEB1 while the normal thyroid cell line expressed the highest levels of E-Cadherin. Quantitative RT-PCR analyses showed that Smad7 mRNA was significantly higher in ATC than in any other group (p<0.05). These results indicate that ATCs show evidence of EMT including decreased expression of E-cadherin and increased expression of ZEB1 compared to well differentiated thyroid carcinomas and that increased expression of Smad7 may be associated with thyroid tumor progression.