Silencing of the tumor suppressor gene SLC5A8 is associated with BRAF mutations in classical papillary thyroid carcinomas
Silencing of the tumor suppressor gene SLC5A8 is associated with BRAF mutations in classical papillary thyroid carcinomas
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DOI：
10.1210/jc.2004-1394
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发表时间：
2005-05-01
影响因子：
5.8
通讯作者：
Rousset, B
中科院分区：
文献类型：
--
作者：
Porra, V;Ferraro-Peyret, C;Rousset, B
SLC5A8被认为是一种甲状腺顶端的碘转运蛋白，最近被定义为短链脂肪酸的钠离子偶联转运蛋白。为了证明SLC5A8在甲状腺中的表达模式，我们分析了其在培养的正常人甲状腺细胞和具有不同功能活性的组织中的表达规律。为了确定SLC5A8在所有甲状腺癌或仅在特定亚型中的表达改变，我们调查了一系列50例功能低下肿瘤中SLC5A8的表达水平。在转录水平上研究SLC5A8的表达，并与SLC26A4或Pendrin和SLC5A5或Na+/碘转运蛋白的表达进行比较。与SLC5A5和SLC26A4不同，SLC5A8在培养的正常人甲状腺细胞中的表达不受TSH的调节，与甲状腺组织的功能状态无关；毒性腺瘤和邻近静止组织的SLC5A8转录本含量相同。SLC5A8在经典型甲状腺乳头状癌(PTC-cf.)中表达选择性下调(40倍)。甲基化特异性聚合酶链式反应分析显示，SLC5A8在90%的PTC-cf中发生甲基化。在其他约20%的乳头状甲状腺癌中。在52例PTC-cf中，SLC5A8的低表达与BRAF T1796A突变的存在密切相关。这些数据证实了抑癌基因SLC5A8的甲基化相关沉默与PTC-cf中BRAF基因的T1796A点突变之间的关系。甲状腺癌的亚型。
SLC5A8, proposed as a thyroid apical iodide transporter, was recently defined as a Na+-coupled transporter of short-chain fatty acid. To document the expression pattern of SLC5A8 in the thyroid, we analyzed the regulation of its expression in normal human thyrocytes in culture and in tissues with distinct functional activity. To determine whether SLC5A8 expression is altered in all thyroid carcinomas or only in particular subtypes, we investigated the level of its expression in a series of 50 hypofunctioning tumors. SLC5A8 expression was studied at the transcript level and compared with that of SLC26A4 or Pendrin and SLC5A5 or Na+/iodide symporter. SLC5A8 expression, unlike that of SLC5A5 and SLC26A4, was not regulated by TSH in normal human thyrocytes in culture and was not related to the functional state of thyroid tissue; toxic adenomas and adjacent resting tissues exhibited the same SLC5A8 transcript content. SLC5A8 expression was selectively down-regulated (40-fold) in papillary thyroid carcinomas of classical form (PTC-cf.). Methylation-specific PCR analyses showed that SLC5A8 was methylated in 90% of PTC-cf. and in about 20% of other papillary thyroid carcinomas. In a series of 52 PTC-cf., a low SLC5A8 expression was highly significantly associated with the presence of BRAF T1796A mutation. These data identify a relationship between the methylation-associated silencing of the tumor-suppressor gene SLC5A8 and the T1796A point mutation of the BRAF gene in the PTC-cf. subtype of thyroid carcinomas.