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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Gene expression and functional evidence of epithelial-to-mesenchymal transition in papillary thyroid carcinoma invasion
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Gene expression and functional evidence of epithelial-to-mesenchymal transition in papillary thyroid carcinoma invasion

机译：甲状腺乳头状癌浸润上皮-间质转化的基因表达和功能证据

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摘要

Papillary thyroid carcinomas (PTCs) that invade into local structures are associated with a poor prognosis, but the mechanisms for PTC invasion are incompletely defined, limiting the development of new therapies. To characterize biological processes involved in PTC invasion, we analyzed the gene expression profiles of microscopically dissected intratumoral samples from central and invasive regions of seven widely invasive PTCs and normal thyroid tissue by oligonucleotide microarray and performed confirmatory expression and functional studies. In comparison with the central regions of primary PTCs, the invasive fronts overexpressed TGF β, NFκB and integrin pathway members, and regulators of small G proteins and CDC42. Moreover, reduced levels of mRNAs encoding proteins involved in cell-cell adhesion and communication were identified, consistent with epithelial-to-mesenchymal transition (EMT). To confirm that aggressive PTCs were characterized by EMT, 34 additional PTCs were examined for expression of vimentin, a hallmark of EMT. Overexpression of vimentin was associated with PTC invasion and nodal metastasis. Functional, in vitro studies demonstrated that vimentin was required both for the development and maintenance of a mesenchymal morphology and inva-siveness in thyroid cancer cells. We conclude that EMT is common in PTC invasion and that vimentin regulates thyroid cancer EMT in vitro.
机译：侵袭局部结构的甲状腺乳头状癌（PTC）与预后不良有关，但PTC侵袭的机制尚未完全确定，限制了新疗法的发展。为了表征参与PTC侵袭的生物学过程，我们通过寡核苷酸微阵列分析了从7个广泛侵袭性PTC的中央和侵袭区域以及正常甲状腺组织中显微解剖的肿瘤内样本的基因表达谱，并进行了确认性表达和功能研究。与初级PTC的中央区域相比，侵袭性前沿过表达TGFβ，NFκB和整联蛋白途径成员，以及小G蛋白和CDC42的调节剂。此外，与上皮-间充质转化（EMT）一致，鉴定出降低水平的编码参与细胞-细胞粘附和交流的蛋白质的mRNA。为了确认EMT具有侵略性PTC的特征，还检查了34种其他PTC的波形蛋白表达，这是EMT的标志。波形蛋白的过表达与PTC侵袭和淋巴结转移有关。体外功能研究表明波形蛋白是甲状腺癌细胞的发展和维持间充质形态和侵袭性所必需的。我们得出结论，EMT在PTC侵袭中很常见，波形蛋白在体外调节甲状腺癌EMT。

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