Dipartimento di Scienze Mediche e Biologiche, Università di Udine, Udine, Italy.
Mol Cell Endocrinol. 2013 Jan 5;365(1):1-10. doi: 10.1016/j.mce.2012.08.019. Epub 2012 Sep 5.
Since PARP-1 is supposed to be part of a multimeric repressor of sodium iodide symporter (NIS) expression, in this study the effect of the PARP inhibitor PJ34 on several properties of thyroid cancer cell lines was investigated. In TPC1, BCPAP, FRO, WRO cell lines PJ34 induced a strong increase in NIS mRNA levels. In BCPAP and TPC1 cells also significant increase of radio-iodine uptake was induced. Accordingly, in transfection experiments performed in TPC1 cells, treatment with PJ34 increased NIS promoter activity without affecting PARP-1 binding to the promoter sequence. We also investigated the epigenetic status of NIS promoter after PJ34 treatment in TPC1 cell line: in addition to an increase of histone modification activation marks (H3K9K14ac, H3K4me3), surprisingly we observed also an increase of H3K27me3, a classical repressive mark. Our data demonstrate that in various thyroid cancer cell lines PARP inhibition increases NIS gene expression through a particular modulation of transcriptional regulatory mechanisms. Therefore, we suggest that PARP inhibitors may deserve future investigations as tools for medical treatment of thyroid cancer.
由于 PARP-1 被认为是钠碘同向转运体（NIS）表达的多聚体抑制剂的一部分，因此在这项研究中，研究了 PARP 抑制剂 PJ34 对几种甲状腺癌细胞系的几种特性的影响。在 TPC1、BCPAP、FRO 和 WRO 细胞系中，PJ34 诱导 NIS mRNA 水平的强烈增加。在 BCPAP 和 TPC1 细胞中，放射性碘摄取也明显增加。因此，在 TPC1 细胞中转染实验中，PJ34 处理增加了 NIS 启动子活性，而不影响 PARP-1 与启动子序列的结合。我们还研究了 TPC1 细胞系中 PJ34 处理后 NIS 启动子的表观遗传状态：除了组蛋白修饰激活标记（H3K9K14ac、H3K4me3）的增加外，令人惊讶的是，我们还观察到 H3K27me3 的增加，这是一种经典的抑制性标记。我们的数据表明，在各种甲状腺癌细胞系中，PARP 抑制通过特定的转录调控机制增加 NIS 基因表达。因此，我们建议 PARP 抑制剂可能值得作为甲状腺癌治疗的工具进行进一步研究。
