Histone Deacetylase Inhibitors Restore Radioiodide Uptake and Retention in Poorly Differentiated and Anaplastic Thyroid Cancer Cells by Expression of the Sodium/Iodide Symporter Thyroperoxidase and Thyroglobulin
| Autor: | Tetsuro Kobayashi, Katsumi Taki, Toyoshi Endo, Toshimasa Onaya, Hideyo Suzuki, Fumihiko Furuya, Kazutaka Haraguchi, Hiroki Shimura, Kazuyasu Ohta |
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| Rok vydání: | 2004 |
| Předmět: |
Sodium-iodide symporter
endocrine system medicine.medical_specialty endocrine system diseases Cell Survival medicine.medical_treatment Gene Expression Mice Nude Iodide Peroxidase Peptides Cyclic Thyroglobulin Iodine Radioisotopes Mice Endocrinology Thyroid peroxidase Cell Line Tumor Depsipeptides Internal medicine medicine Animals Humans RNA Messenger Thyroid Neoplasms Cycloheximide Enzyme Inhibitors Anaplastic thyroid cancer Thyroid cancer Protein Synthesis Inhibitors Symporters biology Chemistry Thyroid medicine.disease Immunohistochemistry Carcinoma Papillary Histone Deacetylase Inhibitors medicine.anatomical_structure Symporter biology.protein |
| Zdroj: | Endocrinology. 145:2865-2875 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2003-1258 |
| Popis: | Iodide uptake by the thyroid is mediated by the sodium/iodide symporter. Upon iodide uptake, thyroperoxidase catalyzes iodination of tyrosine residues in thyroglobulin, retaining iodide within thyroid follicles. Dedifferentiation-induced loss of these functions in cancers, rendering them unresponsive to radioiodide, occurs with most poorly differentiated and anaplastic tumors. We focused on the histone deacetylase (HDAC) inhibitors (HDACI) as a way to induce differentiation of thyroid cancer cells. We assessed re-expression of thyroid-specific genes mRNA induced by HDACI using quantitative RT-PCR and immunostaining in poorly differentiated papillary and anaplastic thyroid cancer cells. HDACI induced expression of thyroid-specific gene mRNAs and proteins, and accumulation of radioiodide through iodination of generic cellular proteins were detected. HDACI-treated tumors could specifically accumulate (125)I as revealed by imaging experiments and radioiodide concentration in vivo. In an attempt to determine the mechanism by which these gene expressions occurred, we detected the inhibition of protein synthesis by cycloheximide, which up-regulated the expression of thyroperoxidase and thyroglobulin mRNA in HDACI-treated cells and down-regulated that of sodium/iodide symporter mRNA. Together, our results suggest that HDACI-induced expression of thyroid-specific genes, some of which is mediated by some protein synthesis, may contribute to development of novel strategy against thyroid cancer. |
| Databáze: | OpenAIRE |
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