Signaling through 3′,5′-cyclic adenosine monophosphate and phosphoinositide-3 kinase induces sodium/iodide symporter expression in breast cancer
Signaling through 3′,5′-cyclic adenosine monophosphate and phosphoinositide-3 kinase induces sodium/iodide symporter expression in breast cancer
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DOI：
10.1210/jc.2004-0907
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发表时间：
2004-10-01
影响因子：
5.8
通讯作者：
Jhiang, SM
中科院分区：
文献类型：
--
作者：
Knostman, KAB;Cho, JY;Jhiang, SM
钠/碘同向转运蛋白（NIS）是一种膜转运糖蛋白，通常在甲状腺和哺乳期乳腺中表达。 NIS 是放射性碘成像和甲状腺癌消融治疗的靶点，并且在乳腺癌治疗中具有类似用途的潜力。为了促进 NIS 介导的放射性核素治疗，有必要确定导致乳腺癌中 NIS 表达和功能增加的信号通路。我们检查了 14 种基因工程小鼠模型的乳腺肿瘤中的 NIS 表达，以确定与 NIS 诱导相关的基因操作。 cAMP 和磷酸肌醇 3 激酶 (PI3K) 信号通路与 NIS 上调相关。我们发现，单独激活 PI3K 足以增加 MCF-7 人乳腺癌细胞中的 NIS 表达和放射性碘摄取，而 cAMP 刺激可增加 NIS 启动子活性和 NIS mRNA 水平，但不足以增加放射性碘摄取。这项研究首次在体内和体外证明乳腺癌中 NIS 表达是由 cAMP 和/或 PI3K 诱导的。
The sodium/iodide symporter (NIS) is a membrane transport glycoprotein normally expressed in the thyroid gland and lactating mammary gland. NIS is a target for radioiodide imaging and therapeutic ablation of thyroid carcinomas and has the potential for similar use in breast cancer treatment. To facilitate NIS-mediated radionuclide therapy, it is necessary to identify signaling pathways that lead to increased NIS expression and function in breast cancer. We examined NIS expression in mammary tumors of 14 genetically engineered mouse models to identify genetic manipulations associated with NIS induction. The cAMP and phosphoinositide-3 kinase (PI3K) signaling pathways are associated with NIS up-regulation. We showed that activation of PI3K alone is sufficient to increase NIS expression and radioiodide uptake in MCF-7 human breast cancer cells, whereas cAMP stimulation increases NIS promoter activity and NIS mRNA levels but is not sufficient to increase radioiodide uptake. This study is the first to demonstrate that NIS expression is induced by cAMP and/or PI3K in breast cancer both in vivo and in vitro.