Petrich T, Knapp W H, Pötter E
Department of Nuclear Medicine, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Nuklearmedizin. 2003 Feb;42(1):15-8.
The sodium/iodide symporter (NIS) actively transports iodide into thyrocytes. Thus, NIS represents a key protein for diagnosis and radioiodine therapy of differentiated thyroid cancer. Additionally, in the future the NIS gene may be used for cancer gene therapy of non-thyroid-derived malignancies. In this study we evaluated the functionality of NIS with respect to iodide uptake in a panel of tumor cell lines and compared this to gene transfer efficiency.
A human NIS-containing expression vector and reporter-gene vectors encoding beta-Galactosidase- or EGFP were used for transient transfection of 13 tumor cell lines. Following transfection measurements of NIS-mediated radioiodide uptake using Na(125)I and of transfection efficiency were performed. The latter included beta-Galactosidase activity measurements using a commercial kit and observation by fluorescence microscopy for EGFP expression.
In contrast to respective parental cells, most NIS-transfected cell lines displayed high, perchlorate-sensitive radioiodide uptake. Differences in radioiodide uptake between cell lines apparently corresponded to transfection efficiencies, as judged from reporter-gene assays.
With respect to iodide uptake we provide evidence that NIS is functional in different cellular context. As iodide uptake capacity appears to be well correlated to gene transfer efficiency, cell type-specific actions on NIS (e. g. post-translational modification such as glycosylation) are not inhibitory to NIS function. Our data support the promising role of NIS in cancer gene therapy strategies.
钠/碘同向转运体（NIS）可将碘主动转运至甲状腺细胞内。因此，NIS是分化型甲状腺癌诊断及放射性碘治疗的关键蛋白。此外，未来NIS基因可能用于非甲状腺来源恶性肿瘤的癌症基因治疗。在本研究中，我们评估了一组肿瘤细胞系中NIS在碘摄取方面的功能，并将其与基因转染效率进行比较。
使用含人NIS的表达载体以及编码β-半乳糖苷酶或增强型绿色荧光蛋白（EGFP）的报告基因载体，对13种肿瘤细胞系进行瞬时转染。转染后，使用Na(125)I测量NIS介导的放射性碘摄取，并检测转染效率。后者包括使用商用试剂盒测量β-半乳糖苷酶活性，以及通过荧光显微镜观察EGFP表达。
与各自的亲本细胞相比，大多数转染NIS的细胞系表现出高的、对高氯酸盐敏感的放射性碘摄取。根据报告基因检测判断，细胞系之间放射性碘摄取的差异显然与转染效率相对应。
关于碘摄取，我们提供证据表明NIS在不同细胞环境中具有功能。由于碘摄取能力似乎与基因转染效率密切相关，对NIS的细胞类型特异性作用（例如翻译后修饰如糖基化）不会抑制NIS功能。我们的数据支持NIS在癌症基因治疗策略中的潜在作用。
