The sodium iodide symporter (NIS): regulation and approaches to targeting for cancer therapeutics.
The sodium iodide symporter (NIS): regulation and approaches to targeting for cancer therapeutics.
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DOI：
10.1016/j.pharmthera.2012.06.007
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发表时间：
2012-09
影响因子：
13.5
通讯作者：
Brent, Gregory A.
中科院分区：
文献类型：
--
作者：
Kogai, Takahiko;Brent, Gregory A.
关键词：
碘化钠同调蛋白（NIS）的表达是甲状腺和哺乳期乳房有效碘吸收所必需的。由于大多数分化的甲状腺癌表达NIS，因此β释放放射性碘通常用于甲状腺全切除术后的残余甲状腺癌和转移。通过高水平的促甲状腺激素刺激NIS的表达是必要的，以实现放射性碘吸收到甲状腺癌，足以进行治疗。大多数乳腺癌也表达NIS，但其表达水平较低，不足以进行放射性碘治疗。维甲酸在某些乳腺癌细胞中是一种有效的NIS诱导剂。NIS在一些非甲状腺组织中也有适度表达，包括唾液腺、泪腺和胃。选择性诱导碘吸收是放射性碘靶向肿瘤所必需的。哺乳动物细胞的碘吸收依赖于NIS基因的表达水平，但也依赖于NIS成功易位到细胞膜并正确插入。NIS表达和膜插入的调节机制受不同组织的信号转导通路的调节。NIS的差异调控可以选择性地诱导甲状腺癌细胞和一些乳腺癌细胞的功能性NIS，从而导致更有效的甲状腺癌放射性碘治疗和乳腺癌治疗的新策略。在肿瘤选择性引入外源性NIS的模型中，已经证明了放射性碘化物系统性治疗一系列不表达内源性NIS的其他癌症的潜力。
Expression of the sodium iodide symporter (NIS) is required for efficient iodide uptake in thyroid and lactating breast. Since most differentiated thyroid cancer expresses NIS, β-emitting radioactive iodide is routinely utilized to target remnant thyroid cancer and metastasis after total thyroidectomy. Stimulation of NIS expression by high levels of thyroid-stimulating hormone is necessary to achieve radioiodide uptake into thyroid cancer that is sufficient for therapy. The majority of breast cancer also expresses NIS, but at a low level insufficient for radioiodine therapy. Retinoic acid is a potent NIS inducer in some breast cancer cells. NIS is also modestly expressed in some non-thyroidal tissues, including salivary glands, lacrimal glands and stomach. Selective induction of iodide uptake is required to target tumors with radioiodide. Iodide uptake in mammalian cells is dependent on the level of NIS gene expression, but also successful translocation of NIS to the cell membrane and correct insertion. The regulatory mechanisms of NIS expression and membrane insertion are regulated by signal transduction pathways that differ by tissue. Differential regulation of NIS confers selective induction of functional NIS in thyroid cancer cells, as well as some breast cancer cells, leading to more efficient radioiodide therapy for thyroid cancer and a new strategy for breast cancer therapy. The potential for systemic radioiodide treatment of a range of other cancers, that do not express endogenous NIS, has been demonstrated in models with tumor-selective introduction of exogenous NIS.
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影响因子：
3.8
作者：
Altorjay A;Dohán O;Szilágyi A;Paroder M;Wapnir IL;Carrasco N
通讯作者：
Carrasco N
影响因子：
4.1
作者：
Chen, H;Juchau, MR
通讯作者：
Juchau, MR
影响因子：
3.1
作者：
Cheong, Su-Jin;Jang, DooRye;Kim, Dong Wook
通讯作者：
Kim, Dong Wook
影响因子：
8
作者：
Boelaert, K.;Smith, V. E.;McCabe, C. J.
通讯作者：
McCabe, C. J.
影响因子：
5.3
作者：
Beardmore, VA;Hinton, HJ;Arthur, JSC
通讯作者：
Arthur, JSC