Notch signaling is involved in expression of thyrocyte differentiation markers and is down-regulated in thyroid tumors
Notch signaling is involved in expression of thyrocyte differentiation markers and is down-regulated in thyroid tumors
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DOI：
10.1210/jc.2008-0528
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发表时间：
2008-10-01
影响因子：
5.8
通讯作者：
Gulino, A.
中科院分区：
文献类型：
--
作者：
Ferretti, E.;Tosi, E.;Gulino, A.
内容：Notch基因编码信号通路的受体，该信号通路在各种情况下调节细胞生长和分化，但Notch信号在甲状腺滤泡细胞中的作用从未完全公开。目的：本研究的目的是表征Notch通路组分在甲状腺滤泡细胞中的表达以及Notch信号在正常和转化的甲状腺细胞中的活性。设计/设置和患者：通过定量RT-PCR和免疫组织化学分析了Notch途径组分和甲状腺细胞分化的关键标志物在小鼠和人甲状腺组织（正常和肿瘤）中的表达。Notch过表达在人甲状腺癌细胞和FTRL-5细胞的影响进行了探讨与分析的基因表达，增殖试验，和实验，涉及转染的荧光素酶报告基因构建含有人NIS promoter regions.Results：Notch受体表达的小鼠甲状腺细胞的发展过程中，其表达水平平行的甲状腺分化标志物。Notch信号也是正常成人甲状腺细胞的特征，并受TSH调节。Notch途径组分在人正常甲状腺组织和甲状腺肿瘤中不稳定表达，但在未分化肿瘤中表达水平明显降低。Notch-1在甲状腺癌细胞中的过表达恢复分化，降低细胞生长速率，并通过对NIS promoter.Conclusion的直接作用刺激NIS表达：Notch信号通路参与甲状腺细胞命运的决定，是甲状腺特异性基因表达的直接调节因子。其失调可能导致与甲状腺肿瘤发生相关的分化丧失。
Context: Notch genes encode receptors for a signaling pathway that regulates cell growth and differentiation in various contexts, but the role of Notch signaling in thyroid follicular cells has never been fully published.Objective: The objective of the study was to characterize the expression of Notch pathway components in thyroid follicular cells and Notch signaling activities in normal and transformed thyrocytes.Design/Setting and Patients: Expression of Notch pathway components and key markers of thyrocyte differentiation was analyzed in murine and human thyroid tissues (normal and tumoral) by quantitative RT-PCR and immunohistochemistry. The effects of Notch overexpression in human thyroid cancer cells and FTRL-5 cells were explored with analysis of gene expression, proliferation assays, and experiments involving transfection of a luciferase reporter construct containing human NIS promoter regions.Results: Notch receptors are expressed during the development of murine thyrocytes, and their expression levels parallel those of thyroid differentiation markers. Notch signaling characterized also normal adult thyrocytes and is regulated by TSH. Notch pathway components are variably expressed in human normal thyroid tissue and thyroid tumors, but expression levels are clearly reduced in undifferentiated tumors. Overexpression of Notch-1 in thyroid cancer cells restores differentiation, reduces cell growth rates, and stimulates NIS expression via a direct action on the NIS promoter.Conclusion: Notch signaling is involved in the determination of thyroid cell fate and is a direct regulator of thyroid-specific gene expression. Its deregulation may contribute to the loss of differentiation associated with thyroid tumorigenesis.