hERG1 channels in human esophagus: Evidence for their aberrant expression in the malignant progression of Barrett's esophagus
hERG1 channels in human esophagus: Evidence for their aberrant expression in the malignant progression of Barrett's esophagus
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DOI：
10.1002/jcp.20748
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发表时间：
2006-11-01
影响因子：
5.6
通讯作者：
Arcangeli, Annarosa
中科院分区：
文献类型：
--
作者：
Lastraioli, Elena;Taddei, Antonio;Arcangeli, Annarosa
离子通道调节广泛的细胞活动。离子通道功能的改变已经在不同的人类病理学中被报道，例如心脏病、神经肌肉病、自身免疫性疾病和癌症。我们研究了hERG 1 K+通道在人上消化道中的表达，重点关注食管下段。特别是，我们分析了逆转录和聚合酶链反应（RT-PCR）和免疫组化（IHC）的内窥镜样品从正常受试者，从患者患有胃食管反流，相关或不与食管炎，并从患者受影响的巴雷特食管（BE），即肠上皮化生。正常样本、胃食管反流症状和反流性食管炎患者样本均不表达hERG 1蛋白。另一方面，69%的BE患者表达hERG 1。由于BE是一种癌前病变，还分析了先前诊断的BE上出现的发育不良（Ds）和腺癌（ADK），所有样本均显示hERG 1蛋白的高表达。对BE患者的监测显示，89%后来发生ADKs的患者显示hERG 1表达。本文报道的数据支持以下假设：hERG 1表达标志着人类食管正常通过化生和异型增生阶段进展为癌症的早期步骤。
Ion channels regulate a broad range of cellular activities. Alteration in ion channel function has been reported in different human pathologies, such as cardiac, neuromuscular, autoimmune diseases, and cancer. We investigated the expression of hERG1 K+ channels in the human upper gastrointestinal tract, focusing our attention on the lower esophagus. In particular, we analyzed by both Reverse transcription and polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) endoscopic samples obtained from normal subjects, from patients suffering from gastroesophageal reflux, associated or not with esophagitis, and from patients affected by Barrett's esophagus (BE), that is, intestinal metaplasia. None of the normal samples, nor those from patients with gastro-esophageal reflux symptoms and reflux esophagitis expressed the hERG1 protein. On the other hand, 69% of patients with BE expressed hERG1. Since BE is a preneoplastic lesion, dysplasias (Ds) and adenocarcinomas (ADKs) arising on a previously diagnosed BE were also analyzed, and all the samples showed a high expression of the hERG1 protein. The surveillance of patients with BE showed that 89% of those who later developed ADKs displayed hERG1 expression. Data here reported, support the hypothesis that hERG1 expression marks an early step of the progression of normality to cancer in the human esophagus through a metaplastic and dysplastic stage.