Expression of pendrin and the Pendred Syndrome (PDS) gene in human thyroid tissues
Expression of pendrin and the Pendred Syndrome (PDS) gene in human thyroid tissues
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DOI：
10.1210/jc.85.5.2028
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发表时间：
2000-05-01
影响因子：
5.8
通讯作者：
Schlumberger, M
中科院分区：
文献类型：
--
作者：
Bidart, JM;Mian, C;Schlumberger, M
最近克隆的Pendred综合征(PDS)基因主要在甲状腺表达，PDS是一种以甲状腺肿大和先天性感音神经性耳聋为特征的常染色体隐性遗传病。它的产品被命名为吊环蛋白，被证明可以运输氯化物和碘化物。为了探讨PDS基因在甲状腺肿瘤发生过程中是否发生改变，我们分别用实时荧光定量聚合酶链式反应和抗肽抗体研究了正常甲状腺组织、良性甲状腺组织和恶性甲状腺组织中PDS基因和Pendrin蛋白的表达。然后将结果与观察到的钠/碘同向转运体(NIS)的表达进行比较。在正常组织中，垂蛋白定位于甲状腺细胞的顶端，这与NIS的基底外侧定位相反。在卵泡内和卵泡间，垂蛋白的免疫染色是不均匀的。在功能亢进的腺瘤中，PDS信使核糖核酸水平在正常范围内，尽管免疫组织化学分析显示大多数滤泡细胞呈强染色。在功能低下的腺瘤中，PDS基因的平均表达与正常甲状腺组织相似，但Pendrin免疫染色的差异很大。在甲状腺癌中，PDS基因表达显著降低，Pendrin免疫组化染色低，仅在罕见的肿瘤细胞中呈阳性。这一表达谱类似于观察到的NIS基因及其蛋白产物。综上所述，我们的研究表明，垂垂蛋白位于甲状腺细胞的顶膜，在甲状腺癌中PDS基因的表达降低。
The gene recently cloned that is responsible for the Pendred syndrome (PDS), an autosomal recessive disease characterized by goiter and congenital sensorineural deafness, is mainly expressed in the thyroid gland. Its product, designated pendrin, was shown to transport chloride and iodide. To investigate whether the PDS gene is altered during thyroid tumorigenesis, PDS gene expression and pendrin expression were studied using real-time kinetic quantitative PCR and antipeptide antibodies, respectively, in normal, benign, and malignant human thyroid tissues. The results were then compared to those observed for sodium/iodide symporter (NIS) expression. In normal tissue, pendrin is localized at the apical pole of thyrocytes, and this in contrast to the basolateral location of NIS. Immunostaining for pendrin was heterogeneous both inside and among follicles. In hyperfunctioning adenomas, the PDS messenger ribonucleic acid level was in the normal range, although immunohistochemical analysis showed strong staining in the majority of follicular cells. In hypofunctioning adenomas, mean PDS gene expression was similar to that detected in normal thyroid tissues, but pendrin immunostaining was highly variable. In thyroid carcinomas, PDS gene expression was dramatically decreased, and pendrin immunostaining was low and was positive only in rare tumor cells. This expression profile was similar to that observed for the NIS gene and its protein product. In conclusion, our study demonstrates that pendrin is located at the apical membrane of thyrocytes and that PDS gene expression is decreased in thyroid carcinomas.