TWIST1 在决定间变性甲状腺癌表型方面起着多效作用。
TWIST1 plays a pleiotropic role in determining the anaplastic thyroid cancer phenotype.
机构信息
Dipartimento di Biologia e Patologia Cellulare e Molecolare c/o Istituto di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Università di Napoli Federico II, 80131 Naples, Italy.
出版信息
J Clin Endocrinol Metab. 2011 May;96(5):E772-81. doi: 10.1210/jc.2010-1182. Epub 2011 Mar 9.
CONTEXT
Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human tumors; it is characterized by chemoresistance, local invasion, and distant metastases. ATC is invariably fatal.
OBJECTIVE
The aim was to study the role of TWIST1, a basic helix-loop-helix transcription factor, in ATC.
DESIGN
Expression of TWIST1 was studied by immunohistochemistry and real-time PCR in normal thyroids and well-differentiated, poorly differentiated, and ATC. The function of TWIST1 was studied by RNA interference in ATC cells and by ectopic expression in well-differentiated thyroid carcinoma cells.
RESULTS
ATCs up-regulate TWIST1 with respect to normal thyroids as well as to poorly and well-differentiated thyroid carcinomas. Knockdown of TWIST1 by RNA interference in ATC cells reduced cell migration and invasion and increased sensitivity to apoptosis. The ectopic expression of TWIST1 in thyroid cells induced resistance to apoptosis and increased cell migration and invasion.
CONCLUSIONS
TWIST1 plays a key role in determining malignant features of the anaplastic phenotype in vitro.
背景
间变性甲状腺癌（ATC）是最具侵袭性的人类肿瘤之一；其特征为化疗耐药、局部浸润和远处转移。ATC 通常是致命的。
目的
本研究旨在探讨 TWIST1（一种碱性螺旋-环-螺旋转录因子）在 ATC 中的作用。
设计
采用免疫组化和实时 PCR 检测 TWIST1 在正常甲状腺、分化良好的甲状腺癌、分化差的甲状腺癌和 ATC 中的表达。通过 RNA 干扰在 ATC 细胞中敲低 TWIST1，通过异位表达在分化良好的甲状腺癌细胞中过表达 TWIST1，研究 TWIST1 的功能。
结果
与正常甲状腺以及分化差和分化良好的甲状腺癌相比，ATC 上调 TWIST1。在 ATC 细胞中通过 RNA 干扰敲低 TWIST1 可降低细胞迁移和侵袭能力，并增加对细胞凋亡的敏感性。在甲状腺细胞中异位表达 TWIST1 可诱导对细胞凋亡的抵抗，增加细胞迁移和侵袭能力。
结论
TWIST1 在体外决定间变表型的恶性特征方面发挥关键作用。
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