Wild-Type P53 Induces Sodium/ Iodide Symporter Expression Allowing Radioiodide Therapy in Anaplastic Thyroid Cancer
Wild-Type P53 Induces Sodium/ Iodide Symporter Expression Allowing Radioiodide Therapy in Anaplastic Thyroid Cancer
复制标题
野生型 P53 诱导钠/碘同向转运蛋白表达，允许放射性碘治疗未分化甲状腺癌
DOI：
10.1159/00048164
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发表时间：
2017
影响因子：
--
通讯作者：
Xiaoping Zhang
中科院分区：
文献类型：
--
作者：
Lin Liu;Dan Li;Zhengqi Chen;Jian Yang;Yushui Ma;Haidong Cai;Chengxiang Shan;Zhongwei Lv;Xiaoping Zhang
目的：甲状腺未分化癌（ATC）是最具侵袭性的实体瘤之一。p53基因突变在甲状腺未分化癌中很常见，但p53突变的影响尚未阐明。在此，我们研究了p53在ATC中的作用。方法：采用免疫组化法检测ATC组织中p53基因突变。采用免疫组化、qRT-PCR、western blot、免疫荧光等方法检测ATC组织和8505 c细胞中NIS的表达。荧光素酶报告基因检测野生型p53对NIS的影响。采用放射性碘摄取实验和流式细胞术分析野生型p53对ATC细胞放射性碘摄取和细胞凋亡的影响。结果：ATC组织中存在p53基因突变。此外，我们证明了野生型p53反式激活NIS启动子。在用野生型p53转染的8505 c细胞中，与携带p53突变的8505 c细胞相比，用放射性碘处理导致放射性碘摄取增加和凋亡细胞死亡增加。结论：转染野生型p53基因可通过调控NIS的表达，增强放射性碘的治疗效果。
Aims: Anaplastic thyroid cancer(ATC) is one of the most aggressive solid tumors. Mutations in the p53 gene are common in anaplastic thyroid cancer, but the effects of p53 mutations are yet to be elucidated. Here, we investigated the role of p53 in ATC. .Methods: p53 mutation was detect by immunohistochemistry in ATC tissues. Expression of NIS were measured usingimmunohistochemistry, qRT-PCR, western blot, immunofluorescence in ATC tissues and cell line 8505c. Luciferase reporter assay was performed to examine the effect of wild-type p53.on NIS. Radioiodide uptake assay and flow cytometry analysis were used to detect the role of wild-type p53 on radioiodide uptake.and cell apoptosis in ATC cell line. .Results: We showed that the p53 mutation can be detected in ATC tissues. Furthermore, we demonstrated that wild-type p53 transactivated the NIS promoter. In 8505c cells transfected with wild-type p53, treatment with radioiodine resulted in increased radioiodine uptake and increased apoptotic.cell death compared with 8505c cells harboring the p53 mutation. .Conclusion: In summary, transfection with wild-type p53 can increase the therapeutic effect of radioiodine by regulating the expression of the NIS.