BACKGROUND AND OBJECTIVES: Sodium-iodine symporter (NIS) is a marker for the degree of differentiation in thyroid cancer. The genetic factors or microenvironment surrounding tumors can affect transcription of NIS. In this study, we investigated the NIS mRNA expression according to mutational status and coexistent lymphocytic thyroiditis in papillary thyroid cancer (PTC). MATERIALS AND METHODS: The RNA expression levels of NIS in the samples from database of The Caner Genome Atlas (TCGA; n=494) and our institute (n=125) were analyzed. RESULTS: The PTCs with the BRAFV600E mutation and the coexistence of BRAFV600E and TERT promoter mutations showed significantly lower expression of NIS (p < 0.001, respectively), and those with BRAF-like molecular subtype also had reduced expression of NIS (p < 0.001). NIS expression showed a positive correlation with thyroid differentiation score (r=0.593, p < 0.001) and negative correlations with expressions of genes involved in ERK signaling (r=−0.164, p < 0.001) and GLUT-1 gene (r=−0.204, p < 0.001). The PTCs with lymphocytic thyroiditis showed significantly higher NIS expression (p=0.013), regardless of mutational status. CONCLUSION: The NIS expression was reduced by the BRAFV600E mutation and MAPK/ERK pathway activation, but restored by the presence of lymphocytic thyroiditis.
Genome ; Ion Transport ; RNA ; RNA, Messenger ; Thyroid Gland ; Thyroid Neoplasms ; Thyroiditis, Autoimmune

The knowledge of gene regulation of serotonin transporter mRNA may provide clues to understanding how antidepressants affect their therapeutic actions. Recently, the effects of antidepressants on the serotonin transporter have been investigated but yielded controversial results. To study this further, we performed in situ hybridization for serotonin transporter mRNA in rats(treatment group, n=5)receiving long term(14 days)treatment with a selective serotonin reuptake inhibiting antidepressant, sertraline(10mg/kg, i.p) Following sertraline treatment, a significant(p<0.05)ncrease in hybridization of serotonin transporter mRNA was observed compared to that observed in vehicle-treated rats(control group, n=5) This result may be interpreted as a compensatory mechanism to reduce synaptic levels of serotonin which were increased by long term sertraline treatment.
Animals ; Antidepressive Agents ; Brain* ; In Situ Hybridization ; Rats* ; RNA, Messenger* ; Serotonin Plasma Membrane Transport Proteins* ; Serotonin* ; Sertraline*

PURPOSE: Cells of mammary gland as well as breast cancer uptake iodide through sodium/iodide symporter (NIS). The pathophysiologic importance of NIS is not evaluated well. The purpose of this study is to find relationships between the expression of NIS and other findings of breast cancer including ER, PR, C-erbB2, topoisomerase IIa, p53, and histologic grade of breast cancer. METHODS: Fresh frozen specimens from 21 female breast cancer patients (mean age 50 13 years) with breast cancer were examined by RT-PCR for NIS mRNA. Immunohistochemical staining for ER, PR, C-erb B2, topoisomerase IIa and p53. Staging and degree of differentiation of cancer cells were also performed to evaluate the biological behavior of breast cancer. RESULTS: NIS mRNA was expressed in 90% of the evaluated breast cancer tissues. The mean semiquantitative value of NIS mRNA in PR positive group was 2.02+/-0.35, which was higher than that of PR negative group (1.11+/-0.18; P=0.001). ER positive group showed higher value of NIS mRNA (2.02+/-0.35) than ER negative group (1.19+/-0.63; P=0.002). In addition, NIS mRNA values was significantly different according to differentiation of cancer cells (well differentiated type, 2.20+/-0.37 vs. less differentiated type, 1.39+/-0.63, P=0.01). However, there was no significant association between NIS mRNA levels and the other biologic characteriscs such as C-erb B2, topoisomerase IIa, and p53. CONCLUSION: The results showed that the expression of NIS in breast cancer may be associated with the presence of PR and ER as well as the degree of differentiation of breast cancer cells.
Breast Neoplasms* ; Breast* ; Female ; Humans ; Ion Transport* ; Mammary Glands, Human ; RNA, Messenger*

Hypertonicity imposes a great deal of stress to cells since it causes rise in cellular ionic strength, which can be reduced by the accumulation of compatible osmolytes. TonEBP plays a central role in the cellular accumulation of compatible osmolytes via transcriptional stimulation of membrane transporters and aldose reductase. Alternatively spliced forms of TonEBP mRNA have previously been reported and two of them showed different transcriptional activity. In the present study, isoform-specific antibodies were produced to confirm the translation of the spliced mRNA to protein. TonEBP was immunoprecipitated by using anti-TonEBP antibody and then immunoblotted using anti-TonEBP or isoform specific antibodies to find out the expression profile of TonEBP isoforms in basal or stimulated condition. From these results, we conclude that all TonEBP isoforms are expressed in mammalian cells and their expression patterns are not same in every cells.
Aldehyde Reductase ; Alternative Splicing ; Antibodies ; Membrane Transport Proteins ; Osmolar Concentration ; Protein Isoforms* ; RNA, Messenger

PURPOSE: Response to radioiodine therapy for thyroid cancer is related to the loss of sodium-iodine symporter protein caused by dedifferentiation of thyroid cancer cells. So we aimed to study mRNA expression of CD97, dedifferentiation marker, and sodium-iodine symporter after retinoic acid treatment according to retinoids receptor status. METHODS: Thyroid cancer cell lines; ARO, FRO, NPA, TPO, and FTC133 were prepared. 5µM of all trans retinoic acid were administered to each cell lines and then expression of m RNA for retinoids receptors (RARα, RARβ, RARγ, RXRα, RXRβ, RXRγ), CD97, and Sodium-Iodine symporter by RT-PCR. RESULTS: RARs and RXRs were differently expressed in each cell line. After retinoic acid treatment, relative density of retinoic acid receptor mRNA were increased by time dependently in each cell line except TPO cell line. Expression of CD97 also was decreased in every cell lines (P<0.001). Retinoic acid increased expression of sodium-iodine symporter only in FTC133 cell line (P<0.001), and TSH or forskolin did not enhance NIS expression by retinoic acid. RARβ and RXRγ were expressed only in FTC 133cell line before treatment. Induction of sodium-iodine symporter by retinoids disappeared after RARβ specific antagonist LE135 or pan RXR antagonist PA452 administration. CONCLUSION: Retinoic acid reduced expression of CD97 in five thyroid cancer cell lines. However, retinoic acid could restore sodium-iodine symporter expression in only FTC 133 cell line specifically containing RARβ and RXRγ. Restoration of sodium-iodine symporter expression by retinoic acid is related to RARβ and RXRγ expression.
Cell Line* ; Colforsin ; Ion Transport* ; Receptors, Retinoic Acid ; Retinoids ; RNA ; RNA, Messenger ; Specific Gravity ; Thyroid Gland* ; Thyroid Neoplasms* ; Tretinoin*

PURPOSE: The present study investigated the dynamics and prognostic role of messenger RNA (mRNA) expression responsible for 18F-fluorodeoxyglucose (FDG) uptake in FDG positron emission tomography (PET) and radioactive iodine (131I) uptake in whole-body radioactive iodine scans (WBS) in papillary thyroid cancer (PTC) patients. MATERIALS AND METHODS: The primary and processed data were downloaded from the Genomic Data Commons Data Portal. Expression data for sodium/iodide symporter (solute carrier family 5 member 5, SLC5A5), hexokinase (HK1–3), glucose-6-phosphate dehydrogenase (G6PD), and glucose transporter (solute carrier family 2, SLC2A1–4) mRNA were collected. RESULTS: Expression of SLC5A5 mRNA were negatively correlated with SLC2A1 mRNA and positively correlated with SLC2A4 mRNA. In PTC with BRAF mutations, expressions of SLC2A1, SLC2A3, HK2, and HK3 mRNA were higher than those in PTC without BRAF mutations. Expression of SLC5A5, SLC2A4, HK1, and G6PD mRNA was lower in PTC without BRAF mutation. PTCs with higher expression of SLC5A5 mRNA had more favorable disease-free survival, but no association with overall survival. CONCLUSION: Expression of SLC5A5 mRNA was negatively correlated with SLC2A1 mRNA. This finding provides a molecular basis for the management of PTC with negative WBS using 18F-FDG PET scans. In addition, higher expression of SLC5A5 mRNA was associated with less PTC recurrence, but not with deaths.
Disease-Free Survival ; Fluorodeoxyglucose F18 ; Genome* ; Glucose Transport Proteins, Facilitative ; Glucosephosphate Dehydrogenase ; Hexokinase ; Humans ; Iodine ; Ion Transport ; Positron-Emission Tomography ; Recurrence ; RNA, Messenger* ; Thyroid Gland* ; Thyroid Neoplasms*

Mammalian mitochondrial genome encodes a small set of tRNAs, rRNAs, and mRNAs. The RNA synthesis process has been well characterized. How the RNAs are degraded, however, is poorly understood. It was long assumed that the degradation happens in the matrix where transcription and translation machineries reside. Here we show that contrary to the assumption, mammalian mitochondrial RNA degradation occurs in the mitochondrial intermembrane space (IMS) and the IMS-localized RNASET2 is the enzyme that degrades the RNAs. This provides a new paradigm for understanding mitochondrial RNA metabolism and transport.
Cell Line ; Humans ; Mitochondrial Membranes ; metabolism ; Protein Transport ; RNA ; biosynthesis ; chemistry ; metabolism ; RNA Stability ; RNA, Mitochondrial ; Ribonucleases ; metabolism ; Tumor Suppressor Proteins ; metabolism

Cadmium intoxication has been associated with the dysregulation of iron homeostasis. In the present study, we investigated the effect of cadmium on the expression of ferroportin 1 (FPN1), an important iron transporter protein that is involved in iron release from macrophages. When we incubated cadmium with J774 mouse macrophage cells, FPN1 mRNA levels were significantly increased in a dose- and time-dependent manner. Furthermore, the cadmium-induced FPN1 mRNA expression was associated with increased levels of FPN1 protein. On the other hand, cadmium-mediated FPN1 mRNA induction in J774 cells was completely blocked when cells were co-treated with a transcription inhibitor, acitomycin D. Also, cadmium directly stimulated the activity of the FPN1-promoter driven luciferase reporter, suggesting that the cadmium up-regulates FPN1 gene expression in a transcription-dependent manner. Finally, cadmium exposure to J774 macrophages increased intracellular reactive oxygen species (ROS) levels by ~ 2-fold, compared to untreated controls. When J774 cells were co-treated with antioxidant N-acetylcystein, the cadmium-induced FPN1 mRNA induction was significantly attenuated. In summary, the results of this study clearly demonstrated that cadmium increased FPN1 expression in macrophages through a mechanism that involves ROS production, and suggests another important interaction between iron and cadmium metabolism.
Animals ; Cadmium ; Cation Transport Proteins ; Gene Expression ; Hand ; Homeostasis ; Iron ; Luciferases ; Macrophages ; Mice ; Reactive Oxygen Species ; RNA, Messenger

BACKGROUN: The sodium-iodide symporter (NIS) is a key plasma membrane glycoprotein that mediates active iodide transport in the thyroid gland. Whereas relatively little is known about the mechanisms by which iodide regulates NIS activity, post-transcriptional events have been suggested to play a role. METHODS: We have attempted to determine the mechanism responsible for the regulation of NIS by determining NIS mRNA and NIS protein levels accompany with measuring NIS activities in FRTL-5 thyroid cells or Sprague-Dawley rats. RESULTS: TSH increased the iodide uptake capacities and the expression of NIS mRNA by time- and concentration-dependent manner. This finding was also true in Sprague-Dawley rats whose serum TSH were elevated by prolonged methimazole administration; the expression of NIS protein was increased in TSH-elevated rats. On the other hands, iodide suppressed the NIS activity by concentration-dependent manner till 1 mM of NaI. But, the amounts of NIS mRNA were not changed, although those were transiently decreased at 24 hours after iodide treatment at the higher concentration of NaI, 10 mM or over. The amounts of NIS protein, which were analyzed by immunohistochemstry, were decreased till first 24 hours, but those were re-increased, the amounts at 48 hours after iodide treatment returned to more than 50% of basal levels. CONCLUSION: TSH induced the expression of NIS, while iodide inhibited the NIS activities. Our finding suggested that the excessive iodide regulates the NIS activity, at least in part, through post-translational as well as transcriptional and translational mechanisms.
Animals ; Cell Membrane ; Glycoproteins ; Hand ; Ion Transport* ; Methimazole ; Rats ; Rats, Sprague-Dawley ; RNA, Messenger ; Thyroid Gland* ; Thyrotropin

BACKGROUND: Iodide has been known to control the function and the growth of the thyroid gland, and to be used as a substrate of thyroid hormone. Moreover, it has been suggested that excessive iodide stimulates the thyroid autoimmune responses. To evaluate the effects of iodide on thyrocytes, we investigated cell function and proliferation, or thyroid autoantigen expression after administering iodide to rats or FRTL-5 cells. MEHTODS AND RESULTS: Ten-weeks-old Sprague-Dawley rats were sacrificed after 7 days of NaI treatment. The expressions of thyroid autoantigens were examined by northern blot analysis. Chronic administration of iodide resulted in no effect on TSH receptor (TSHR) and thyroperoxidase (TPO) mRNA expression, while it increased thyroglobulin (TG) and diminished sodium-iodide symporter (NIS) mRNA expression. FRTL-5 cells were also treated with various concentrations of NaI. The generation of cAMP or iodide uptake was decreased, and the cellular growth was also inhibited by iodide. However, the expressions of all thyroid autoantigens (TSHR, TG, TPO, MHC class I and class II) except NIS were unchanged for 72 hours after iodide administration. The expression of NIS was mildly increased after 24 hours. CONCLUSION: Iodide resulted in decreased cell proliferation and cellular function of cAMP generation and iodide uptake. Chronic administration of iodide increased TG and diminished NIS mRNA expression in vivo but not in vitro
Animals ; Autoantigens* ; Autoimmunity ; Blotting, Northern ; Cell Proliferation ; Ion Transport ; Rats ; Rats, Sprague-Dawley ; Receptors, Thyrotropin ; RNA, Messenger ; Thyroglobulin ; Thyroid Gland*