T3 enhances thyroid cancer cell proliferation through TRβ1/Oct-1-mediated cyclin D1 activation
T3 enhances thyroid cancer cell proliferation through TRβ1/Oct-1-mediated cyclin D1 activation
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DOI：
10.1016/j.mce.2013.10.001
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发表时间：
2014-01-25
影响因子：
4.1
通讯作者：
Ando, Sebastiano
中科院分区：
文献类型：
--
作者：
Perri, Anna;Catalano, Stefania;Ando, Sebastiano
一些研究表明，甲状腺激素T3促进癌细胞生长，尽管参与这一过程的分子机制仍有待阐明。在这项研究中，我们证明了T3诱导甲状腺乳头状癌细胞系增殖的同时，cyclin D1的表达上调，而cyclin D1是一个关键的有丝分裂原调节的细胞周期控制元件。我们的数据显示，T3增强了cyclin D1启动子内octmer -转录因子-1位点上TR β 1/Oct-1复合物的募集，导致其反式激活。此外，通过RNA干扰沉默TR β 1或Oct-1表达可逆转细胞增殖增加和细胞周期蛋白D1上调，揭示这两种转录因子在介导这些作用中的重要作用。最后，在敲低cyclin D1表达后，t3诱导的细胞生长增加被消除。这些发现突出了T3促进甲状腺癌细胞生长的一种新的分子机制。2013爱思唯尔爱尔兰有限公司版权所有。
Several studies have demonstrated that thyroid hormone T3 promotes cancer cell growth, even though the molecular mechanism involved in such processes still needs to be elucidated. In this study we demonstrated that T3 induced proliferation in papillary thyroid carcinoma cell lines concomitantly with an up-regulation of cyclin D1 expression, that is a critical mitogen-regulated cell-cycle control element. Our data revealed that T3 enhanced the recruitment of the TR beta 1/Oct-1 complex on Octamer-transcription factor-1 site within cyclin D1 promoter, leading to its transactivation. In addition, silencing of TR beta 1 or Oct-1 expression by RNA interference reversed both increased cell proliferation and up-regulation of cyclin D1, underlying the important role of both transcriptional factors in mediating these effects. Finally, T3-induced increase in cell growth was abrogated after knocking down cyclin D1 expression. All these findings highlight a new molecular mechanism by which T3 promotes thyroid cancer cell growth. (C) 2013 Elsevier Ireland Ltd. All rights reserved.