钠碘同向转运体基因介导放射性碘治疗肿瘤的研究进展

钠碘同向转运体(NIS)作为一种细胞膜蛋白,主要存在于甲状腺滤泡细胞基底膜并介导细胞的碘转运,在甲状腺癌及非甲状腺癌的放射性碘治疗研究中备受关注.部分甲状腺癌的NIS表达水平降低或者膜蛋白定位不好,通过导入NIS基因进行膜表达,介导核素滞留于细胞内,是肿瘤治疗的新途径.但目前主要存在核素在细胞内滞留时间短而影响疗效的问题.对此,在导入NIS基因后,可通过各种方法刺激肿瘤细胞增加NIS的功能性表达而增加核素的摄取,也可通过减少核素的流出来提高其滞留,扩展NIS基因治疗的应用范围,优化肿瘤治疗.该文主要综述了NIS基因介导的肿瘤治疗研究进展.     

钠/碘同向转运体

钠 /碘同向转运体是甲状腺滤泡细胞基底细胞膜上的糖蛋白 ,介导甲状腺对碘的主动运输。本文综述钠 /碘同向转运体在基因、蛋白质二级结构、电生理学特征、调控及组织分布等方面的进展 ,及其对甲状腺疾病和放射性碘治疗的意义。     

Sodium iodide symporter: its role in nuclear medicine.

Thyroid iodide uptake is basic to the clinical applications of radioiodine. Iodide uptake occurs across the membrane of the thyroid follicular cells through an active transporter process mediated by the sodium iodide symporter (NIS). The recent cloning of the NIS gene enabled the better characterization of the molecular mechanisms underlying iodide transport, thus opening the way to the clarification and expansion of its role in nuclear medicine. In papillary and follicular carcinoma, NIS immunostaining was positive in only a few tumor cells, and no NIS protein expression was detected in anaplastic carcinomas. Decreased NIS expression levels account for the reduced iodide uptake in thyroid carcinomas. Thus, by targeting NIS expression in cancer cells, we could enable these cells to concentrate iodide from plasma and in so doing offer the possibility of radioiodine therapy. Several investigators have shown that gene transfer of NIS into a variety of cell types confers increased radioiodine uptake by up to several hundredfold that of controls in nonthyroid cancers as well as in thyroid cancer. In addition, my group proposes that NIS may serve as an alternative imaging reporter gene in addition to the HSVtk and dopaminergic receptor genes. The NIS has the potential to expand the role of nuclear medicine in the future, just as it has served as the base for the development of nuclear medicine in the past.     

Efficacy of lentiviral-mediated transfection of hTSHR in poorly differentiated thyroid carcinoma cell line

IntroductionDedifferentiated thyroid cancer is often incurable because it does not respond to radioiodine. This study aimed to investigate iodide uptake and the expressions of thyroid-specific molecules after the transfection of human thyrotropin receptor (hTSHR) gene in poorly differentiated follicular thyroid cancer cell line (FTC-133).MethodspGC-FU-hTSHR-GFP-lentivirus and pGC-FU-GFP-lentivirus were added into FTC-133 cells respectively. The parental cells were defined as the blank group. Cells transduced with pGC-FU-GFP and pGC-FU-hTSHR-GFP were defined as the control group and experimental group respectively. The efficiency of transfection was observed under a fluorescence microscope. ¹²⁵I uptake by FTC-133 was analyzed by measuring the radioactivity. Real time-PCR, western blotting and radioimmunoassay were applied to detect the expressions of mRNAs and proteins of Na⁺/I^? symporter (NIS), thyroid-stimulating hormone receptor (TSHR), thyroid peroxidase (TPO) and thyroglobulin (Tg) in FTC-133.ResultsThe green fluorescence was present in 80% of the transduced cells under fluorescence microscope. The iodine uptake of cells transduced with pGC-FU-TSHR-GFP was 3.3 times higher than that in the other two groups (P < 0.01). NIS, TSHR, TPO and Tg had been significantly up-regulated in the experimental group as compared to the control group (P < 0.01) and the blank group (P < 0.01).ConclusionThe hTSHR transfection in FTC-133 improved the expression of thyroid-specific molecules including TSHR, NIS, TPO and Tg and radioiodide uptake.     

Sodium Iodide Symporter and the Radioiodine Treatment of Thyroid Carcinoma

Since the specific accumulation of iodide in thyroid was found in 1915, radioiodine has been widely applied to diagnose and treat thyroid cancer. Iodide uptake occurs across the membrane of the thyroid follicular cells and cancer cells through an active transporter process mediated by the sodium iodide symporter (NIS). The NIS coding genes were cloned and identified from rat and human in 1996. Evaluation of the NIS gene and protein expression is critical in the management of thyroid cancer, and several approaches have been tried to increase NIS levels. Identification of the NIS gene has provided a means of expanding its role in the radionuclide gene therapy of nonthyroidal cancers as well as thyroid cancer. In this article, we explain the relationship between NIS expression and the treatment of thyroid carcinoma with I-131, and we include a review of the results of our experimental and clinical trials.     

Relationship between expression of the sodium/iodide symporter and 131I uptake in recurrent lesions of differentiated thyroid carcinoma

The sodium/iodide symporter (NIS) is known to be responsible for the active accumulation of iodide within the thyroid gland. We evaluated the relationship between the expression of NIS in primary or lymph node lesions and iodine-131 uptake in recurrent lesions of differentiated thyroid cancer. In 67 patients with differentiated thyroid cancer (5 follicular and 62 papillary carcinomas), the expression of NIS was analysed by immunohistochemical staining using polyclonal antibodies against human NIS. We used paraffin block tissues of primary tumours or metastatic lesions, and also assessed ¹³¹I uptake in recurrent lesions of thyroid cancer on postoperative ¹³¹I whole-body scan. Immunohistochemical staining was positive in 22 patients (32.8%), including 2 of 5 follicular and 20 of 62 papillary carcinomas. Recurrence was confirmed in 40 patients pathologically or clinically by serum thyroglobulin, ¹³¹I scan, fluorine-18 fluorodeoxyglucose positron emission tomography and/or computed tomography. Among these 40 patients, 28 showed positive uptake on ¹³¹I scan. Fourteen tumour specimens out of 28 (50%) were positive by NIS immunohistochemical staining. The remaining 12 patients with recurrent cancer showed negative ¹³¹I scans, and all specimens were negative by NIS immunohistochemical staining. Thus, NIS immunohistochemical staining predicted ¹³¹I uptake in recurrent cancer with a 100% positive predictive value and a 46.2% negative predictive value. There was no difference in the positivity of NIS according to the site of recurrence on ¹³¹I scan. Outcome of ¹³¹I therapy could be assessed in 22 of the 28 patients who showed ¹³¹I uptake in recurrent lesions. Patients with positive NIS immunostaining responded to ¹³¹I therapy better than did patients with negative immunostaining (P<0.05). In conclusion, NIS immunohistochemical staining showed a high positive predictive value in predicting iodine uptake. Positive immunohistochemical staining of human NIS in primary or lymph node lesions may predict ¹³¹I accumulation and effectiveness of ¹³¹I therapy in recurrent lesions.     

钠/碘同向转运体在甲状腺癌131Ⅰ治疗中的应用

钠/碘同向转运体(Na+/I-symporter,NIS)是一种膜蛋白,介导甲状腺滤泡细胞的碘转运,在甲状腺癌的病理生理及131Ⅰ治疗中起着重要的作用.多数研究表明,甲状腺癌的NIS mRNA及蛋白表达水平降低;维甲酸、去甲基化及组蛋白脱乙酰酶抑制剂可刺激失分化甲状腺癌细胞的NIS表达,为甲状腺癌.131Ⅰ的有效治疗进行了有益的探索.NIS基因的克隆和其特性的揭示为甲状腺癌的靶向基因放射治疗提供了可能.     

曲古菌素A对甲状腺癌细胞NIS基因表达和摄碘功能的影响

目的探讨曲古菌素A（TSA）对甲状腺癌细胞中钠／碘同向转运蛋白（NIS）基因表达和摄取碘的影响。方法以不同浓度的TSA诱导滤泡状甲状腺癌细胞FFC-133及乳头状甲状腺癌细胞K1,利用反转录-聚合酶链反应（RT—PCR）分析经诱导后2株甲状腺癌细胞中NISmRNA的表达,以NIS／3-磷酸甘油醛脱氢酶（GAPDH）的条带密度比值作为mRNA表达强度,并检测诱导前后甲状腺癌细胞对放射性碘摄取的变化。2组数据间比较采用独立样本t检验,多组数据间比较用One．wayANONA方差分析。结果20,50,75,100和150nmol／LTSA诱导48h后,甲状腺癌细胞FFC-133的NISmRNA表达较未诱导对照组增加了1．5至13．7倍,各TSA浓度组间FTC-133NISmRNA表达差异有统计学意义（F=32．56,P〈0．01）;而K1的NISmRNA表达没有明显变化,TSA浓度为50和75nmol／L时表达有所增加（NIS／GAPDH条带密度比值分别为0．62±0．16,0．60±0．23）,但与对照组（O．41±0．18）比较差异无统计学意义（F=2．823,P〉0．05）。细胞摄取碘实验显示,50和75nmol／LTSA诱导48h后,FTC-133的摄碘增加[（15．42±0．42）×10’和（18．98±1．33）×10^3计数·min^-1／10^5个细胞],与对照组[（8．46±0．84）×10^3计数·min^-1／10%5个细胞]比较,差异有统计学意义（t值分别为3．018和3．557,P均〈0．05）;而50和75nmol／LTSA作用后K1对碘的摄取也有增加[（5．83±1．09）×10^3和（6．97±0．65）×10^3计数·min^-1／10^5个细胞],但与对照组[（5．37±0．88）×10^3计数·min^-1／10^5个细胞]比较,差异无统计学意义（t值分别为0．185和0．332,P均〉0．05）。结论TSA能明显诱导滤泡状甲状腺癌细胞的NISmRNA表达升高和摄碘增加,而对乳头状甲状腺癌细胞作用不明显。     

Expression Patterns of Glucose Transporter-1 Gene and Thyroid Specific Genes in Human Papillary Thyroid Carcinoma

Purpose

The expression of glucose transporter-1 (Glut-1) gene and those of major thyroid-specific genes were examined in papillary carcinoma tissues, and the expressions of these genes were compared with cancer differentiation grades.

Materials and Methods

Twenty-four human papillary carcinoma tissues were included in this study. The expressions of Glut-1- and thyroid-specific genes [sodium/iodide symporter (NIS), thyroid peroxidase, thyroglobulin, TSH receptor and pendrin] were analyzed by RT-PCR. Expression levels were expressed as ratios versus the expression of beta-actin. Pathologic differentiation of papillary carcinoma was classified into a relatively well-differentiated group (n = 13) and relatively less differentiated group (n = 11).

Results

Glut-1 gene expression was significantly higher in the less differentiated group (0.66 ± 0.04) than in the well-differentiated group (0.59 ± 0.07). The expression levels of the NIS, PD and TG genes were significantly higher in the well-differentiated group (NIS: 0.67 ± 0.20, PD: 0.65 ± 0.21, TG: 0.74 ± 0.16) than in the less differentiated group (NIS: 0.36 ± 0.05, PD: 0.49 ± 0.08, TG: 0.60 ± 0.11), respectively. A significant negative correlation was found between Glut-1 and NIS expression, and positive correlations were found between NIS and TG, and between NIS and PD.

Conclusion

The NIS, PD and TG genes were highly expressed in well-differentiated thyroid carcinomas, whereas the Glut-1 gene was highly expressed in less differentiated thyroid carcinomas. These findings provide a molecular rationale for the management of papillary carcinoma, especially in the selection of FDG PET or radioiodine whole-body scan and I-131-based therapy.     

Relationship between expression of the sodium/iodide symporter and 131I uptake in recurrent lesions of differentiated thyroid carcinoma

The sodium/iodide symporter (NIS) is known to be responsible for the active accumulation of iodide within the thyroid gland. We evaluated the relationship between the expression of NIS in primary or lymph node lesions and iodine-131 uptake in recurrent lesions of differentiated thyroid cancer. In 67 patients with differentiated thyroid cancer (5 follicular and 62 papillary carcinomas), the expression of NIS was analysed by immunohistochemical staining using polyclonal antibodies against human NIS. We used paraffin block tissues of primary tumours or metastatic lesions, and also assessed 131I uptake in recurrent lesions of thyroid cancer on post-operative 131I whole-body scan. Immunohistochemical staining was positive in 22 patients (32.8%), including 2 of 5 follicular and 20 of 62 papillary carcinomas. Recurrence was confirmed in 40 patients pathologically or clinically by serum thyroglobulin, 131I scan, fluorine-18 fluorodeoxyglucose positron emission tomography and/or computed tomography. Among these 40 patients, 28 showed positive uptake on 131I scan. Fourteen tumour specimens out of 28 (50%) were positive by NIS immunohistochemical staining. The remaining 12 patients with recurrent cancer showed negative 131I scans, and all specimens were negative by NIS immunohistochemical staining. Thus, NIS immunohistochemical staining predicted 131I uptake in recurrent cancer with a 100% positive predictive value and a 46.2% negative predictive value. There was no difference in the positivity of NIS according to the site of recurrence on 131I scan. Outcome of 131I therapy could be assessed in 22 of the 28 patients who showed 131I uptake in recurrent lesions. Patients with positive NIS immunostaining responded to 131I therapy better than did patients with negative immunostaining (P<0.05). In conclusion, NIS immunohistochemical staining showed a high positive predictive value in predicting iodine uptake. Positive immunohistochemical staining of human NIS in primary or lymph node lesions may predict 131I accumulation and effectiveness of 131I therapy in recurrent lesions.     

Predictive role of nontumoral sodium iodide symporter activity and preoperative thyroid characteristics in remission process of thyroid cancer patients

Objective

The target of radioiodine ablation therapy (RIAT) after complete tumor removal is the nontumoral remnant tissue. We aimed to evaluate sodium iodide symporter (NIS) expression in nontumoral thyroid tissue in differentiated thyroid cancer (DTC) patients who have complete but delayed structural response (DSR) to RIAT after surgery. Preoperative thyroid characteristics such as volume and nontumoral histology were also investigated for both DSR and its control group as potential predictors of insufficient NIS activity in this study.

Methods

Total of 600 patients with postoperative remnant thyroid tissue and who were in remission after RIAT spontaneously, were included in the study. Patients with positive diagnostic whole body scan (DxWBS) with thyroid bed uptake and stimulated serum Tg level <2 ng/mL at first year visit after initial therapy were defined as DSR group. Immunohistochemical staining of NIS protein was performed on the nontumoral tissue sections from surgery and semi quantified in terms of density and intensity. DSR and its control group were also compared in terms of NIS expression, radioiodine (RAI) uptake on post-therapy scan and preoperative thyroid characteristics.

Results

When compared with the control group, the density and intensity of NIS expression as well as the intensity of RAI uptake were significantly lower in DSR group (p = 0.001). There were also significant differences between groups regarding preoperative thyroid characteristics; i.e. preoperative thyroid volumes were significantly higher and the presence of concurrent benign thyroid disease was significantly more common in DSR group (p = 0.035, p = 0.001). Hashimoto thyroiditis was 8.59 times higher (95 % CI; 2.31–31.96) and multinodular goiter was 7.50 times higher (95 % CI; 1.88–29.91) among DSR group when compared with the control group.

Conclusions

Our findings suggest that insufficient NIS activity in nontumoral thyroid tissue associates with DSR in DTC patients who have postoperative remnant tissue. Preoperative thyroid characteristics such as volume and concomitant benign thyroid disease may have an important role in predicting the complete response time to RIAT in these patients.     

重组质粒hTSHR转染低分化甲状腺癌细胞株后对摄碘能力及特异性基因表达的影响

目的 探讨重组真核表达质粒pcDNA3.1/人TSH受体（hTSHR）体外转染TSHR表达下降的低分化滤泡状甲状腺癌细胞株后,细胞摄取放射性碘功能以及甲状腺癌相关基因mRNA表达 的变化.方法 pcDNA3.1/hTSHR转化DH5a感受态菌,进行扩增、酶切,再以核苷酸测序方法鉴定.体外转染pcDNA3.1/hTSHR,通过免疫荧光检测TSHR表达产物,井型γ计数仪检测摄碘率,相对定量实时荧光PCR验证其表达的TSHR蛋白功能和特性.采用SPSS 13.0软件,对计量资料行t检验.结果pcDNA3.1/hTSHR经PCR扩增hTSHR-cDNA片段约113 kb,Kpn Ⅰ和Xha Ⅰ双酶切：hTSHR-cDNA的片段约2.3 kb,pcDNA3.1（＋）的片段约5.5 kb,均同预期片段大小相符;核苷酸测序方法鉴定测序结果与GenBank中收录的hTSHR全长序列一致,表明真核表达质粒构建正确.在hTSH刺激下,转染pcDNA3.1/hTSHR细胞与转染pcDNA3.1（＋）细胞比较：（1）在甲状腺肿瘤细胞胞质、胞膜有增强的绿色荧光,（2）前者125 I摄取率是后者的2.9倍（t=28.63,P＜0.01）,（3）甲状腺碘摄取相关基因TSHR、钠碘转运体（NIS）、甲状腺过氧化物酶（TPO）、Tg的mRNA的表达分别升高1.74倍（t=5.959,P＜0.01）、7.2倍（t=3.807,P＜0.05）、2.88倍（t=4.769,P＜0.01）和2.67倍（t=6.388,P＜0.01）.结论 pcDNA3.1/hTSHR体外转染甲状腺癌肿瘤细胞后,可有效提高碘的摄取;这可为放射性碘治疗失分化甲状腺癌提供新的实验依据.     

Kinetics of perrhenate uptake and comparative biodistribution of perrhenate, pertechnetate, and iodide by NaI symporter-expressing tissues in vivo.

Pertechnetate (as (99m)TcO(4)(-)), (123)I(-), and (131)I(-) have a long and successful history of use in the diagnosis and therapy of thyroid cancer, with uptake into thyroid tissue mediated by the sodium-iodide symporter (NIS). NIS has also emerged as a potential target for radiotherapy of nonthyroid malignancies that express the endogenous or transfected symporter. Perrhenates (as (188)ReO(4)(-) and (186)ReO(4)(-)) are promising therapeutic substrates of NIS, although less is known about their behavior in vivo. In this study, we endeavored to characterize the biologic behavior of perrhenate, especially in relation to iodide and pertechnetate, to better explore its possible therapeutic role. METHODS: We describe the simultaneous biodistribution and uptake in vivo of iodide, pertechnetate, and perrhenate in groups of healthy CD1 mice, either with or without coadministration of perchlorate (ClO(4)(-)), a potent NIS inhibitor. Animals administered single radiopharmaceuticals were imaged as a means of illustrating these findings. Kinetic properties of perrhenate were compared with those of iodide in a stably transfected NIS-bearing Madin-Darby canine kidney (MDCK) cell line. RESULTS: Biodistributions of iodide, pertechnetate, and perrhenate in live mice were remarkably similar. Activity in salivary gland and stomach was severalfold greater than in blood, remained elevated over the initial 2 h, and subsequently washed out. A similar pattern characterized pertechnetate and perrhenate uptake by the thyroid, in which the 2-h concentration was slightly more elevated than at the 20-min time point. However, uptake subsequently decreased by 19 h. In contrast, iodide continued to increase through the 19-h time point, presumably as a result of organification. The addition of perchlorate sharply decreased uptake of all 3 radiopharmaceuticals by the stomach, salivary glands, and thyroid and resulted in their rapid clearance, paralleling blood-pool clearance. In tissues that do not express NIS (liver, muscle, spleen), uptake of all 3 radiopharmaceuticals was low and rapidly decreased over time, paralleling blood-pool clearance. Similar findings were seen in kidney, where only minimal amounts of NIS are expressed in tubular cells. In stably transfected MDCK cells, steady-state accumulation of iodide was approximately 4-fold higher than that of perrhenate at 30 min. No active transport was demonstrated in nontransfected MDCK cell lines or after perchlorate administration. Uptake values measured at different concentrations of substrate demonstrated saturation kinetics. Apparent maximal velocity values for perrhenate and iodide were 25.6 +/- 1.4 and 106 +/- 3.2 pmol/ micro g, respectively, and corresponding affinity constant values were 4.06 +/- 0.87 and 24.6 +/- 1.81 micro mol/L. CONCLUSION: Perrhenate is avidly taken up by NIS in a manner similar to iodide and pertechnetate in vivo, with the exception of organification of iodide by the thyroid. By more fully appreciating the behavior of perrhenate, especially in relation to iodide and pertechnetate, we can better realize its potential role in the diagnosis and therapy of NIS-bearing tissues.     

甲状腺癌术后131I治疗

甲状腺癌确诊后，经典的治疗方法是近全切除术后加131I治疗。研究表明，NIS(钠／碘同向转运体)具有聚碘能力，而TPO(甲状腺过氧化物酶)能抑制碘从细胞中流出，NIS和TPC基因联合转染肿瘤细胞介导~(131)I治疗有可能成为一种新的治疗方法；维加酸可诱导失分化肿瘤细胞的摄碘能力恢复或提高，也有利于~(131)I治疗。     

The Effect of Tanespimycin (17-AAG) on Radioiodine Accumulation in Sodium-Iodide Symporter Expressing Cells

Purpose

The heat shock protein 90 inhibitor, tanespimycin, is an anticancer agent known to increase iodine accumulation in normal and cancerous thyroid cells. Iodine accumulation is regulated by membrane proteins such as sodium iodide symporter (NIS) and pendrin (PDS), and thus we attempted to characterize the effects of tanespimycin on those genes.

Methods

Cells were incubated with tanespimycin in order to evaluate ¹²⁵I accumulation and efflux ability. Radioiodine uptake and efflux were measured by a gamma counter and normalized by protein amount. RT-PCR were performed to measure the level of gene expression.

Results

After tanespimycin treatment, ¹²⁵I uptake was increased by ∼2.5-fold in FRTL-5, hNIS-ARO, and hNIS-MDA-MB-231 cells, but no changes were detected in the hNIS-HeLa cells. Tanespimycin significantly reduced the radioiodine efflux rate only in the FRTL-5 cells. In the FRTL-5 and hNIS-ARO cells, PDS mRNA levels were markedly reduced; the only other observed alteration in the levels of NIS mRNA after tanespimycin treatment was an observed increase in the hNIS-ARO cells.

Conclusions

These results indicate that cellular responses against tanespimycin treatment differed between the normal rat thyroid cells and human cancer cells, and the reduction in the ¹²⁵I efflux rate by tanespimycin in the normal rat thyroid cells might be attributable to reduced PDS gene expression.     

钠/碘同向转运体与放射性碘治疗

钠/碘同向转运体(NIS)是一种调节甲状腺及其他组织碘转运活性的膜蛋白。NIS在甲状腺的病理生理中发挥着关键性作用,它实现了甲状腺组织摄取碘并进行甲状腺激素的生物合成,实现了甲状腺功能亢进和分化型甲状腺癌的显像诊断和放射性碘治疗。近年来,对NIS的进一步分子学研究表明,NIS有可能对甲状腺及非甲状腺肿瘤的诊断和放射性碘治疗产生更加深远的影响。     

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.     

Sodium Iodide Symporter (NIS) in the Management of Patients with Thyroid Carcinoma

Although radioiodine has been applied in thyroid diseases including carcinoma for over 70 years, it was only in 1996 that the basic molecular mechanism of iodine uptake was identified. Iodide is actively transported into the thyroid via a membrane glycoprotein known as sodium iodide symporter (NIS). NIS mediates radioiodine uptake into thyroid normal and cancer cells. The knowledge on NIS expression has provided scientific background to the empirical management of thyroid carcinoma. Based on recent studies of the NIS gene, this paper provides current clinical applications and future studies.     

重组NIS基因腺相关病毒的制备及其在甲状腺癌细胞系表达

目的探讨钠碘同向转运体（NIS）基因介导的甲状腺癌基因治疗的可行性。方法构建腺相关病毒载体质粒pGA—NIS，并采用磷酸钙沉淀法制备重组NIS基因的腺相关病毒rAAV—NIS，体外感染甲状腺癌细胞系FTC-133、8505C后，通过免疫荧光检测被感染细胞的NIS蛋白表达，并通过摄碘实验及NaClO4摄碘抑制实验验证其表达的NIS蛋白功能和特性。结果成功制备了重组NIS基因的rAAV—NIS，其感染肿瘤细胞所表达的NIS蛋白位于细胞膜上，且具有介导碘摄取的功能，以及被NaClO4抑制的特性，表明与正常甲状腺细胞的NIS具有相同的功能和特性。感染细胞的碘摄取较未感染细胞明显增高。结论rAAV—NIS能介导甲状腺癌细胞的碘摄取，为甲状腺癌NIS基因介导的基因治疗提供了实验依据。