Thyroid hormone is a MAPK-dependent growth factor for thyroid cancer cells and is anti-apoptotic (Retracted article. See vol. 195, 2023)
Thyroid hormone is a MAPK-dependent growth factor for thyroid cancer cells and is anti-apoptotic (Retracted article. See vol. 195, 2023)
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DOI：
10.1016/j.steroids.2006.11.014
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发表时间：
2007-02-01
期刊：
影响因子：
2.7
通讯作者：
Davis, Faith B.
中科院分区：
文献类型：
--
作者：
Lin, Hung-Yun;Tang, Heng-Yuan;Davis, Faith B.
通过增殖细胞核抗原（PCNA）检测，甲状腺激素（l -甲状腺素，T-4，或3,5,3'-三碘- l -甲状腺原氨酸，T-3）对人乳头状和滤泡状甲状腺癌细胞系的处理导致细胞增殖增强。甲状腺激素也诱导Ras/MAPK （ERK-1/2）信号转导通路的激活。碘甲状腺原氨酸类似物tetraiodothyroacetic acid （tetrac）可抑制碘甲状腺原氨酸与整合素alphaVbeta3上甲状腺激素细胞表面受体的结合，从而阻断甲状腺激素引起的ERK1/2活化和细胞增殖。MAPK级联抑制剂PD 98059也能阻断激素诱导的细胞增殖。然后我们评估了甲状腺激素抗细胞凋亡的可能性。我们首先证实了白藜芦醇（10 μ M），一种在其他癌细胞中促凋亡的药物，在乳头状和滤泡状甲状腺癌细胞中诱导p53依赖性凋亡和c-fos， c-jun和p21基因表达。二苯乙烯诱导细胞凋亡需要p53的Ser-15磷酸化。白藜芦醇诱导的基因表达和细胞凋亡被生理浓度的T4抑制50%以上。在没有白藜芦醇的情况下，T4激活了MAPK，导致p53的Ser-15磷酸化最小，并且不影响c-fos， c-jun和p21 mRNA的丰度。因此，甲状腺激素通过质膜激活MAPK级联可促进体外甲状腺乳头状和滤泡状癌细胞的增殖。(c) 2006爱思唯尔公司版权所有。
Thyroid hormone (L-thyroxine, T-4, or 3,5,3'-triiodo-L-thyronine, T-3) treatment of human papillary and follicular thyroid cancer cell lines resulted in enhanced cell proliferation, measured by proliferating cell nuclear antigen (PCNA). Thyroid hormone also induced activation of the Ras/MAPK (ERK-1/2) signal transduction pathway. ERK1/2 activation and cell proliferation caused by thyroid hormone were blocked by an iodothyronine analogue, tetraiodothyroacetic acid (tetrac), that inhibits binding of iodothyronines to the cell surface receptor for thyroid hormone on integrin alphaVbeta3. A MAPK cascade inhibitor at MEK, PD 98059, also blocked hormone-induced cell proliferation. We then assessed the possibility that thyroid hormone is anti-apoptotic. We first established that resveratrol (10 mu M), a pro-apoptotic agent in other cancer cells, induced p53-dependent apoptosis and c-fos, c-jun and p21 gene expression in both papillary and follicular thyroid cancer cells. Induction of apoptosis by the stilbene required Ser-15 phosphorylation of p53. Resveratrol-induced gene expression and apoptosis were inhibited more than 50% by physiological concentrations of T4. T4 activated MAPK in the absence of resveratrol, caused minimal Ser-15 phosphorylation of p53 and did not affect c-fos, c-jun and p21 mRNA abundance. Thus, plasma membrane-initiated activation of the MAPK cascade by thyroid hormone promotes papillary and follicular thyroid cancer cell proliferation in vitro. (c) 2006 Elsevier Inc. All rights reserved.