Jeong Hwanjeong, Kim Yu-Ri, Kim Ki-Nam, Choe Jae-Gol, Chung June-Key, Kim Meyoung-Kon
Department of Nuclear Medicine, College of Medicine, Wonkwang University, Iksan, Jellabuk-do 570-711, South Korea.
Nucl Med Biol. 2006 Oct;33(7):875-82. doi: 10.1016/j.nucmedbio.2006.07.004.
The plasma membrane glycoprotein sodium/iodide symporter (NIS) is crucial for thyroid hormone biosynthesis and mediates the iodide uptake of thyrocytes. It has been shown that retinoic acid (RA) alters NIS gene expression in thyroid carcinoma lines and stimulates their iodide uptake. Here, we generated an ARO human thyroidal cancer cell line that expresses the NIS gene (ARO-NIS) and found that its baseline 125I uptake was threefold higher than that of its parental ARO cells. However, a 1-microM all-trans retinoic acid (tRA) treatment significantly increased this 125I uptake up to approximately approximately 6.5-fold on Day 3. tRA also elevated NIS mRNA expression in ARO-NIS cells, with peaks of expression being observed on Day 3. To investigate the underlying genomic mechanisms involved in these tRA-induced phenotypic changes, we subjected tRA-treated and untreated ARO-NIS cells to cDNA microarray analysis. Of 1152, genes spotted onto the microarray membrane, 18 were up-regulated (z ratio>2.0) and 33 were down-regulated (z ratio<-2.0) in ARO-NIS cells after 3 days of tRA treatment. More specifically, tRA increased the expression of BCL3, CSRP3, v-fos, and CDK5 genes and decreased the expression of the FGF12 and IGFBP6 genes. Thus, tRA treatment of human anaplastic thyroid carcinoma cells stably expressing the NIS gene significantly elevates their NIS-mediated radioiodine uptake and alters the expression of many genes involved in cell growth and cellular differentiation. Therefore, tRA treatment and NIS gene transfection are potential tools for the diagnosis and treatment of thyroid cancer.
质膜糖蛋白钠/碘同向转运体（NIS）对甲状腺激素的生物合成至关重要，并介导甲状腺细胞摄取碘。研究表明，视黄酸（RA）可改变甲状腺癌细胞系中NIS基因的表达，并刺激其碘摄取。在此，我们构建了一种表达NIS基因的ARO人甲状腺癌细胞系（ARO-NIS），发现其基线125I摄取量比亲代ARO细胞高三倍。然而，在第3天，1 μM全反式视黄酸（tRA）处理显著增加了这种125I摄取，达到约6.5倍。tRA还提高了ARO-NIS细胞中NIS mRNA的表达，在第3天观察到表达峰值。为了研究这些tRA诱导的表型变化所涉及的潜在基因组机制，我们对tRA处理和未处理的ARO-NIS细胞进行了cDNA微阵列分析。在微阵列膜上点样的1152个基因中，tRA处理3天后，ARO-NIS细胞中有18个基因上调（z值>2.0），33个基因下调（z值<-2.0）。更具体地说，tRA增加了BCL3、CSRP3、v-fos和CDK5基因的表达，并降低了FGF12和IGFBP6基因的表达。因此，用tRA处理稳定表达NIS基因的人未分化甲状腺癌细胞可显著提高其NIS介导的放射性碘摄取，并改变许多参与细胞生长和细胞分化的基因的表达。因此，tRA处理和NIS基因转染是甲状腺癌诊断和治疗的潜在工具。
