The plasma membrane glycoprotein sodium/iodide symporter (NIS) is crucial for thyroid hormone biosynthesis and mediates the iodide uptake of thyrocytes. It has been shown that retinoic acid (RA) alters NIS gene expression in thyroid carcinoma lines and stimulates their iodide uptake. Here, we generated an ARO human thyroidal cancer cell line that expresses the NIS gene (ARO-NIS) and found that its baseline 125I uptake was threefold higher than that of its parental ARO cells. However, a 1-μM all-trans retinoic acid (tRA) treatment significantly increased this 125I uptake up to approximately ∼6.5-fold on Day 3. tRA also elevated NIS mRNA expression in ARO-NIS cells, with peaks of expression being observed on Day 3. To investigate the underlying genomic mechanisms involved in these tRA-induced phenotypic changes, we subjected tRA-treated and untreated ARO-NIS cells to cDNA microarray analysis. Of 1152, genes spotted onto the microarray membrane, 18 were up-regulated (z ratio>2.0) and 33 were down-regulated (z ratio<-2.0) in ARO-NIS cells after 3 days of tRA treatment. More specifically, tRA increased the expression of BCL3, CSRP3, v-fos, and CDK5 genes and decreased the expression of the FGF12 and IGFBP6 genes. Thus, tRA treatment of human anaplastic thyroid carcinoma cells stably expressing the NIS gene significantly elevates their NIS-mediated radioiodine uptake and alters the expression of many genes involved in cell growth and cellular differentiation. Therefore, tRA treatment and NIS gene transfection are potential tools for the diagnosis and treatment of thyroid cancer.
Bibliographical noteFunding Information:
We are grateful to Dr. Yoon S. Cho-Chung (Cellular Biochemistry Section, Basic Research Laboratory, CCR, National Cancer Institute, National Institutes of Health, Bethesda, MD) and Dr. Kevin G. Becker (DNA Array Unit, NIA, National Institutes of Health) for their valuable advice about cDNA microarrays. This study was supported by grants from the National Nuclear Technology Program, Basic Research Program and Medical Research Center for Environmental Toxicogenomics and Proteomics, funded by the Korea Science and Engineering Foundation and the Ministry of Science and Technology (nos. M20504040001-05A0704-00112, R01-2001-000-00212-0 and R01-2003-016-01002-0). In addition, this study was supported by two grants from the Korea Health 21 R&D Project, funded by the Ministry of Health and Welfare (HMP-00-GN-01-0002 and KPGRN-R-04).
- Gene expression profile
- Nuclear medicine
- Radioiodine therapy
- Retinoid acid
- Sodium/iodide symporter (NIS)
- Thyroid cancer
ASJC Scopus subject areas
- Molecular Medicine
- Radiology Nuclear Medicine and imaging
- Cancer Research