Liu Lin, Li Dan, Chen Zhengqi, Yang Jian, Ma Yushui, Cai Haidong, Shan Chengxiang, Lv Zhongwei, Zhang Xiaoping
Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
Department of Institution of Interventional and Vascular Surgery, Tongji University, Shanghai, China.
Cell Physiol Biochem. 2017;43(3):905-914. doi: 10.1159/000481640. Epub 2017 Sep 29.
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.
p53 mutation was detect by immunohistochemistry in ATC tissues. Expression of NIS were measured using immunohistochemistry, 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.
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.
In summary, transfection with wild-type p53 can increase the therapeutic effect of radioiodine by regulating the expression of the NIS.
间变性甲状腺癌（ATC）是最具侵袭性的实体瘤之一。p53基因的突变在间变性甲状腺癌中很常见，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。
采用免疫组织化学法检测ATC组织中的p53突变。利用免疫组织化学、qRT-PCR、蛋白质印迹法、免疫荧光法检测ATC组织和细胞系8505c中NIS的表达。进行荧光素酶报告基因检测以检查野生型p53对NIS的影响。采用放射性碘摄取试验和流式细胞术分析检测野生型p53对ATC细胞系放射性碘摄取和细胞凋亡的作用。
我们发现ATC组织中可检测到p53突变。此外，我们证明野生型p53可反式激活NIS启动子。与携带p53突变的8505c细胞相比，在转染野生型p53的8505c细胞中，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。
总之，转染野生型p53可通过调节NIS的表达提高放射性碘的治疗效果。
