TAZ/WWTR1 is overexpressed in papillary thyroid carcinoma
TAZ/WWTR1 is overexpressed in papillary thyroid carcinoma
复制标题
DOI：
10.1016/j.ejca.2010.11.008
复制
发表时间：
2011-04-01
影响因子：
8.4
通讯作者：
Zannini, Mariastella
中科院分区：
文献类型：
--
作者：
de Cristofaro, Tiziana;Di Palma, Tina;Zannini, Mariastella
在这项研究中，我们分析了转录共激活因子TAZ（带pdz结合基序的转录共激活因子），也被称为WWTR1，在一组甲状腺乳头状癌样本中的表达，我们观察到其在此类肿瘤中的表达显著降低。具体来说，通过实时定量PCR (qRT-PCR)，我们评估了甲状腺乳头状癌（PTC）组织标本（n = 61）中TAZ mRNA的水平，我们发现PTC样本中TAZ mRNA的表达水平远高于正常甲状腺组织（p < 0.001）。通过免疫组化分析，对正常甲状腺（n = 10）和病理甲状腺（n = 17）的TAZ表达进行了评估，证实了PTC中TAZ蛋白水平升高。为了进一步分析PTC中TAZ过表达的分子机制，我们使用了一个由FRTL-5大鼠甲状腺细胞组成的诱导系统，该系统表达条件RAS癌蛋白，我们发现RAS信号通路的激活参与了TAZ的解除。这些观察结果表明，RAS/RAF/MEK（丝裂原活化蛋白激酶）/ERK（细胞外信号调节激酶）信号通路的激活效应物参与了TAZ表达的增加，支持了这可能也发生在甲状腺乳头状癌中的观点。此外，我们证明了TAZ的过表达能够在培养中赋予甲状腺细胞生长优势，并诱导上皮-间质转化。总之，这些发现支持TAZ在甲状腺乳头状癌发病机制中的潜在作用。(C) 2010 Elsevier Ltd.版权所有。
In this study, we analysed the expression of the transcriptional coactivator TAZ (transcriptional co-activator with PDZ-binding motif), also named WWTR1, in a panel of papillary thyroid carcinoma samples and we observed a significant deregulation of its expression in such tumours. Specifically, by quantitative real-time PCR (qRT-PCR) we evaluated TAZ mRNA levels in tissue specimens (n = 61) of papillary thyroid carcinoma (PTC) and herein we show that the PTC samples express much higher TAZ mRNA levels with respect to the normal thyroid tissue (p < 0.001). TAZ expression was also evaluated in normal (n = 10) and pathological human thyroids (n = 17) by immunohistochemical analysis and the increase of TAZ protein levels in PTC was confirmed. To further analyse the molecular mechanisms underlying TAZ overexpression in PTC, we used an inducible system consisting of FRTL-5 rat thyroid cells expressing a conditional RAS oncoprotein and we show that the activation of the RAS signalling pathway is involved in TAZ deregulation. These observations suggest that the activated effectors of the RAS/RAF/MEK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) signalling pathway are involved in the increased expression of TAZ, supporting the idea that this may also occur in thyroid papillary carcinoma. Moreover, we demonstrated that the overexpression of TAZ is able to confer growth advantage to thyroid cells in culture and to induce epithelial-mesenchymal transition. In conclusion, these findings support a potential role for TAZ in the pathogenesis of papillary thyroid carcinomas. (C) 2010 Elsevier Ltd. All rights reserved.