Overexpression of NDRG2 Increases Iodine Uptake and Inhibits Thyroid Carcinoma Cell Growth In Situ and In Vivo.
Overexpression of NDRG2 Increases Iodine Uptake and Inhibits Thyroid Carcinoma Cell Growth In Situ and In Vivo.
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NDRG2 的过表达可增加碘摄取并抑制甲状腺癌细胞原位和体内生长
DOI：
10.3727/096504015x14452563486093
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发表时间：
2016-01-21
影响因子：
3.1
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Yin A;Wang C;Sun J;Gao J;Tao L;Du X;Zhao H;Yang J;Li Y
甲状腺髓样癌是一种起源于甲状腺神经内分泌C细胞的罕见的高度侵袭性神经内分泌系统肿瘤。除了手术切除，没有太多有效的全身治疗MTC的选择。N-Myc下游调节基因2（NDRG 2）在MTC中的表达明显低于正常甲状腺组织。然而，NDRG 2在MTC肿瘤发生中的功能在很大程度上是未知的。在这项研究中，我们发现，NDRG 2的过表达抑制TT细胞（人甲状腺髓样癌细胞）在体外的增殖和抑制MTC在裸鼠异种移植模型的发展。进一步分析发现NDRG 2可使TT细胞阻滞于G 0/G1期，并诱导TT细胞凋亡。此外，NDRG 2过表达可能通过降低细胞周期蛋白D1和细胞周期蛋白E蛋白水平介导抗增殖作用。我们还发现异常NDRG 2减轻TT细胞迁移和体外侵袭。钠/碘同向转运体（NIS）介导主动I-转运进入甲状腺滤泡细胞，放射性核素治疗是MTC的一种有前途的治疗方法。我们目前的数据显示，NDRG 2过表达增强了TT细胞中的NIS水平，并增加了体外碘摄取。此外，异种移植肿瘤的99 mTcO 4 −放射性核素成像表明NDRG 2可以促进NIS介导的放射性核素转运。总之，NDRG 2是MTC生物学行为调控的关键分子，是放射性碘治疗的潜在促进剂。
Medullary thyroid carcinoma (MTC) is an uncommon and highly aggressive tumor of the neuroendocrine system, which derives from the neuroendocrine C cells of the thyroid gland. Except for surgical resection, there are not very many effective systemic treatment options for MTC. N-Myc downstream-regulated gene 2 (NDRG2) had a significantly lower expression in MTC compared with normal thyroid tissue. However, the function of NDRG2 in MTC oncogenesis is largely unknown. In this study, we found that overexpression of NDRG2 inhibited the proliferation of TT cells (human medullary thyroid carcinoma cells) in vitro and suppressed the development of MTC in a nude mouse xenograft model. Further analysis revealed that NDRG2 arrested the cell cycle G0/G1 phase progression and induced TT cell apoptosis. Moreover, NDRG2 overexpression may mediate the antiproliferative effect by reducing cyclin D1 and cyclin E protein levels. We also found aberrant NDRG2-mitigated TT cell migration and invasion in vitro. Sodium/iodide symporter (NIS) mediates active I− transport into the thyroid follicular cells, and radionuclide treatment is a promising therapy for MTC. Our current data revealed that NDRG2 overexpression enhanced NIS level in TT cells and increased their iodine uptake in vitro. Furthermore, 99mTcO4 − radionuclide imaging of the xenograft tumors indicated that NDRG2 could promote NIS-mediated radionuclide transport. In conclusion, the present study suggested that NDRG2 is a critical molecule in the regulation of MTC biological behavior and a potential promoter in radioactive iodine therapy.