Chiefari Eusebio, Brunetti Antonio, Arturi Franco, Bidart Jean-Michel, Russo Diego, Schlumberger Martin, Filetti Sebastiano
Department of Clinical Sciences, University of Roma La Sapienza, Roma, Italy.
BMC Cancer. 2002 Dec 10;2:35. doi: 10.1186/1471-2407-2-35.
Sodium/iodide symporter (NIS) is a key protein in iodide transport by thyroid cells and this activity is a prerequisite for effective radioiodide treatment of thyroid cancer. In the majority of thyroid cancers, however, iodide uptake is reduced, probably as a result of decreased NIS protein expression.
To identify the mechanisms that negatively affect NIS expression in thyroid tumors, we performed electrophoresis mobility shift assays and immunoblot analysis of nuclear protein extracts from normal and tumoral thyroid tissues from 14 unrelated patients.
Two proteins closely related to the transcription factors AP2 and Sp1 were identified in the nuclear extracts. Expression of both AP2 and Sp1 in nuclear extracts from thyroid tumors was significantly higher than that observed in corresponding normal tissues.
These observations raise the possibility that NIS expression, and subsequently iodide transport, are reduced in thyroid tumors at least in part owing to alterations in the binding activity of AP2 and Sp1 transcription factors to NIS promoter.
钠/碘同向转运体（NIS）是甲状腺细胞碘转运的关键蛋白，该活性是甲状腺癌有效放射性碘治疗的前提条件。然而，在大多数甲状腺癌中，碘摄取减少，这可能是由于NIS蛋白表达降低所致。
为了确定对甲状腺肿瘤中NIS表达产生负面影响的机制，我们对14名无关患者的正常和肿瘤甲状腺组织的核蛋白提取物进行了电泳迁移率变动分析和免疫印迹分析。
在核提取物中鉴定出两种与转录因子AP2和Sp1密切相关的蛋白。甲状腺肿瘤核提取物中AP2和Sp1的表达均显著高于相应正常组织中的表达。
这些观察结果提示，甲状腺肿瘤中NIS表达以及随后的碘转运减少，至少部分是由于AP2和Sp1转录因子与NIS启动子的结合活性改变所致。
