Effect of all-trans retinoic acid on sodium/iodide symporter expression, radioiodine uptake and gene expression profiles in a human anaplastic thyroid carcinoma cell line.
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-microM all-trans retinoic acid (tRA) treatment significantly increased this 125I uptake up to approximately 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.
Jeong
Hwanjeong
H
Department of Nuclear Medicine, College of Medicine, Wonkwang University, Iksan, Jellabuk-do 570-711, South Korea.
Kim
Yu-Ri
YR
Kim
Ki-Nam
KN
Choe
Jae-Gol
JG
Chung
June-Key
JK
Kim
Meyoung-Kon
MK
D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate / Q000187:drug effects; D009363:Neoplasm Proteins / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D027981:Symporters / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism*; D014212:Tretinoin / Q000008:administration & dosage*; D000099209:Sodium-Iodide Symporters
D007457:Iodine Radioisotopes; D009363:Neoplasm Proteins; D019275:Radiopharmaceuticals; D027981:Symporters; D014212:Tretinoin; D000099209:Sodium-Iodide Symporters