title: Overexpression of NDRG2 Increases Iodine Uptake and Inhibits Thyroid Carcinoma Cell Growth In Situ and In Vivo.
abstract: 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, (99m)TcO4(-) 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an, China.
authors.forename: Anqi
authors.initials: A
authors.lastname: Yin
authors.forename: Chengguo
authors.initials: C
authors.lastname: Wang
authors.forename: Jiachen
authors.initials: J
authors.lastname: Sun
authors.forename: Jianjun
authors.initials: J
authors.lastname: Gao
authors.forename: Liang
authors.initials: L
authors.lastname: Tao
authors.forename: Xilin
authors.initials: X
authors.lastname: Du
authors.forename: Huadong
authors.initials: H
authors.lastname: Zhao
authors.forename: Jiandong
authors.initials: J
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D063646:Carcinogenesis / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015870:Gene Expression; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism / Q000493:pharmacokinetics*; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000378:metabolism / Q000493:pharmacokinetics*; D013670:Sodium Pertechnetate Tc 99m / Q000493:pharmacokinetics; D027981:Symporters / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D000099209:Sodium-Iodide Symporters
chemical_list: D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D013670:Sodium Pertechnetate Tc 99m; D027981:Symporters; D025521:Tumor Suppressor Proteins; D000099209:Sodium-Iodide Symporters; C466228:NDRG2 protein, human