The glial fibrillary acidic protein promoter directs sodium/iodide symporter gene expression for radioiodine therapy of malignant glioma

Abstract Context: Active placental transport of maternal iodide by the thyroidal sodium iodide symporter (NIS) provides an essential substrate for fetal thyroid hormone synthesis. NIS is expressed in trophoblast and is regulated by human choriogonadotropin (hCG). In thyroid, iodide down-regulates expression of several genes including NIS. Placentas of iodine-deficient rats demonstrate up-regulation of NIS mRNA, suggesting a role for iodide in regulating placental NIS. Objectives and Methods: The objectives were to examine effects of iodide on expression of NIS and hCG in BeWo choriocarcinoma cells. Gene expression was studied by quantitative real-time PCR. Effects on NIS protein expression were assessed by Western blotting. Functional activity of NIS was measured by 125I uptake. Expression of hCG protein was assessed by immunoassay of secreted hormone. Results: Iodide inhibited NIS mRNA and membrane protein expression as well as 125I uptake, which were paralleled by decreased βhCG mRNA expression and protein secretion. Iodide had no effects on pendrin expression. Addition of hCG increased NIS mRNA expression. This effect was partially inhibited by addition of iodide. The inhibitory effects of iodide on NIS mRNA expression were abolished by propylthiouracil and dithiothreitol. Conclusions: We conclude that expression of placental NIS is modulated by maternal iodide. This may occur through modulation of hCG effects on NIS and hCG gene expression.

Download Full-text

Sequential Changes in Glial Fibrillary Acidic Protein and Gene Expression Following Parasagittal Fluid-Percussion Brain Injury in Rats

Journal of Neurotrauma ◽

10.1089/neu.1999.16.567 ◽

1999 ◽

Vol 16 (7) ◽

pp. 567-581 ◽

Cited By ~ 38

Author(s):

W. DALTON DIETRICH ◽

JESSIE TRUETTNER ◽

WEIZHAO ZHAO ◽

OFELIA F. ALONSO ◽

RAUL BUSTO ◽

...

Keyword(s):

Gene Expression ◽

Brain Injury ◽

Glial Fibrillary Acidic Protein ◽

Acidic Protein ◽

Fluid Percussion

Download Full-text

Evaluation of Lentiviral-Mediated Expression of Sodium Iodide Symporter in Anaplastic Thyroid Cancer and the Efficacy of In Vivo Imaging and Therapy

Journal of Oncology ◽

10.1155/2011/178967 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Chien-Chih Ke ◽

Ya-Ju Hsieh ◽

Luen Hwu ◽

Fu-Hui Wang ◽

Fu-Du Chen ◽

...

Keyword(s):

Gene Expression ◽

Sodium Iodide ◽

Cell Function ◽

Tumor Imaging ◽

Promising Result ◽

Anaplastic Thyroid Cancer ◽

Anaplastic Thyroid Carcinoma ◽

Sodium Iodide Symporter

Anaplastic thyroid carcinoma (ATC) is one of the most deadly cancers. With intensive multimodalities of treatment, the survival remains low. ATC is not sensitive to131I therapy due to loss of sodium iodide symporter (NIS) gene expression. We have previously generated a stable human NIS-expressing ATC cell line, ARO, and the ability of iodide accumulation was restored. To make NIS-mediated gene therapy more applicable, this study aimed to establish a lentiviral system for transferring hNIS gene to cells and to evaluate the efficacy of in vitro and in vivo radioiodide accumulation for imaging and therapy. Lentivirus containing hNIS cDNA were produced to transduce ARO cells which do not concentrate iodide. Gene expression, cell function, radioiodide imaging and treatment were evaluated in vitro and in vivo. Results showed that the transduced cells were restored to express hNIS and accumulated higher amount of radioiodide than parental cells. Therapeutic dose of131I effectively inhibited the tumor growth derived from transduced cells as compared to saline-treated mice. Our results suggest that the lentiviral system efficiently transferred and expressed hNIS gene in ATC cells. The transduced cells showed a promising result of tumor imaging and therapy.

Download Full-text