Retinoic acid increases sodium/iodide symporter mRNA levels in human thyroid cancer cell lines and suppresses expression of functional symporter in nontransformed FRTL-5 rat thyroid cells
Retinoic acid increases sodium/iodide symporter mRNA levels in human thyroid cancer cell lines and suppresses expression of functional symporter in nontransformed FRTL-5 rat thyroid cells
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DOI：
10.1006/bbrc.1997.7715
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发表时间：
1997-11-26
影响因子：
3.1
通讯作者：
Kohrle, J
中科院分区：
文献类型：
--
作者：
Schmutzler, C;Winzer, R;Kohrle, J
去分化甲状腺癌中碘摄入量的减少阻碍了放射性碘治疗。 RT-PCR 分析显示，与正常甲状腺相比，人类甲状腺癌中 Na+/I- 同向转运体 (NIS) mRNA 的表达降低。然而，在滤泡性甲状腺癌细胞系FTC-133和FTC-238中，用1μM全反式视黄酸(RA)处理显着增加NIS mRNA水平。未分化甲状腺癌细胞系 HTh74 和 C643 显示 NIS mRNA 的基础表达，但没有 RA 刺激。通过蛋白质印迹判断，所有四种细胞系均含有与 80 kD NIS 相似的蛋白，尽管它们不积累碘化物。相反，在未转化的大鼠FRTL-5细胞中，1μM RA下调NIS mRNA水平，在TSH耗尽后抑制TSH或毛喉素触发的NIS信息诱导，并在5天后将碘摄取量降低至38%。 NIS 的这种不同的 RA 反应性可能提供了一种方法，通过上调碘化物转运到肿瘤组织中，同时抑制正常甲状腺细胞中碘化物的积累，从而将放射性碘靶向甲状腺癌，从而重新建立放射性碘治疗的潜力。 (C) 1997 年学术出版社。
Decreased iodide uptake in de-differentiated thyroid carcinomas impedes radioiodide therapy. RT-PCR analysis revealed reduced expression of Na+/I- symporter (NIS) mRNA in human thyroid carcinomas as compared to normal thyroid. However, in follicular thyroid carcinoma cell lines FTC-133 and FTC-238, treatment with 1 mu M all-trans retinoic acid (RA) markedly increased NIS mRNA levels. Anaplastic thyroid carcinoma cell lines HTh74 and C643 showed basal expression of NIS mRNA, but no RA-stimulation. All four cell lines contained the similar to 80 kD NIS protein as judged by Western blot, although they did not accumulate iodide. In contrast, in nontransformed rat FRTL-5 cells, 1 mu M RA downregulated NIS mRNA levels, inhibited the TSH- or forskolin-triggered induction of NIS message after TSH-depletion, and reduced iodide uptake to 38% after 5 d. This divergent RA-responsivity of NIS may provide the means to target radioiodide to thyroid carcinomas by upregulating iodide transport into tumor tissue while simultaneously inhibiting iodide accumulation in normal thyrocytes and may thus re-establish the potential for radioiodide therapy. (C) 1997 Academic Press.