T3 enhances thyroid cancer cell proliferation through TR尾1/Oct-1-mediated cyclin D1 activation

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• 作者：Anna Perri ; Stefania Catalano ; Daniela Bonofiglio ; Donatella Vizza ; Daniela Rovito ; Hongyan Qi ; Saveria Aquila ; Salvatore Panza ; Pietro Rizza ; Marilena Lanzino ; Sebastiano And貌
• 关键词：TH ; thyroid hormone ; TRs ; thyroid hormone receptors ; TR尾1 ; thyroid hormone receptor 尾1 ; Oct-1 ; Octamer-transcription factor-1 ; CycD1 ; cyclin D1
• 刊名：Molecular and Cellular Endocrinology
• 出版年：25 January, 2014
• 年：2014
• 卷：382
• 期：1
• 页码：205-217
• 全文大小：1322 K

文摘

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尾1/Oct-1 complex on Octamer-transcription factor-1 site within cyclin D1 promoter, leading to its transactivation. In addition, silencing of TR尾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.