Expression of Smad4 and Smad7 in human thyroid follicular carcinoma cell lines
Expression of Smad4 and Smad7 in human thyroid follicular carcinoma cell lines
复制标题
DOI：
10.1007/bf03345213
复制
发表时间：
2003-06-01
影响因子：
5.4
通讯作者：
Kimura, ET
中科院分区：
文献类型：
--
作者：
Cerutti, JM;Ebina, KN;Kimura, ET
Smad蛋白已被证明介导转化生长因子β (tgfβ)下游的信号转导途径。tgfβ诱导Smad2和Smad3磷酸化，它们与Smad4结合并转运到细胞核，在那里它们调节基因转录；除了这些刺激性的smad外，抑制性smad， Smad6和Smad7，通过阻断受体和中断Smads2/3的磷酸化来对抗信号传导。由于tgf - β信号元件Smad4失活而导致的tgf - β敏感性丧失是多种人类疾病（包括癌症）的基础。此外，在一些疾病中发现了抑制Smad7的过表达，它可以阻止Smad2/3的磷酸化，从而抑制TGFbeta信号通路。本研究采用RT-PCR和免疫细胞化学方法研究了Smad4和Smad7在甲状腺细胞系（NPA乳头状癌、WRO滤泡癌和ARO间变性癌）中的表达。我们的研究结果表明，Smad4在所有甲状腺细胞系和对照组中表达，与Smad4表达缺失的其他类型肿瘤不同。另一方面，Smad7在恶性甲状腺滤泡癌ARO间变性细胞系中过表达。我们的数据表明，Smad7过表达消除TGFbeta反应可能是未分化甲状腺肿瘤中观察到的肿瘤侵袭性的机制。
Smad proteins have been shown to mediate the signal transduction pathway downstream of the transforming growth factor beta (TGFbeta). TGFbeta induces the phosphorylation of Smad2 and Smad3 which associate with Smad4 and translocate to the nucleus where they regulate gene transcription; besides these stimulatory Smads, the inhibitory Smads, Smad6 and Smad7, oppose signaling by blocking receptors and interrupting the phosphorylation of Smads2/3. The loss of TGFbeta-sensitivity, caused by inactivation of components of TGFbeta signaling, as Smad4, underlies a wide variety of human disorders, including cancer. In addition, the overexpression of the inhibitory Smad7, which prevents the phosphorylation of Smad2/3 and consequently inhibits TGFbeta signaling pathways, was ob-served in some diseases. In the present study we investigated the expression of Smad4 and Smad7 in thyroid cell lines (NPA papillary carcinoma, WRO follicular carcinoma and ARO anaplastic carcinoma) by RT-PCR and immunocytochemistry. Our results show that Smad4 was expressed in all thyroid cell lines and controls analyzed, differently from other classes of tumors where Smad4 expression was deleted. On the other hand, Smad7 was overexpressed in ARO anaplastic cell line, the most malignant follicular thyroid carcinoma. Our data suggest that the abrogation of the TGFbeta response by Smad7 overexpression may be a mechanism for the tumor aggressiveness observed in undifferentiated thyroid tumors.