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首页> 外文期刊>British Journal of Cancer >hERG1 channels drive tumour malignancy and may serve as prognostic factor in pancreatic ductal adenocarcinoma
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hERG1 channels drive tumour malignancy and may serve as prognostic factor in pancreatic ductal adenocarcinoma

机译：hERG1通道可驱动肿瘤恶性肿瘤，并可作为胰腺导管腺癌的预后因素

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Background: hERG1 channels are aberrantly expressed in human cancers. The expression, functional role and clinical significance of hERG1 channels in pancreatic ductal adenocarcinoma (PDAC) is lacking. Methods: hERG1 expression was tested in PDAC primary samples assembled as tissue microarray by immunohistochemistry using an anti-hERG1 monoclonal antibody ( α -hERG1-MoAb). The functional role of hERG1 was studied in PDAC cell lines and primary cultures. ERG1 expression during PDAC progression was studied in Pdx-1-Cre,LSL-Kras ~( G12D/+ ) ,LSL-Trp53 ~( R175H/+ )transgenic ( KPC ) mice. ERG1 expression in vivo was determined by optical imaging using Alexa-680-labelled α -hERG1-MoAb. Results: (i) hERG1 was expressed at high levels in 59% of primary PDAC; (ii) hERG1 blockade decreased PDAC cell growth and migration; (iii) hERG1 was physically and functionally linked to the Epidermal Growth Factor-Receptor pathway; (iv) in transgenic mice, ERG1 was expressed in PanIN lesions, reaching high expression levels in PDAC; (v) PDAC patients whose primary tumour showed high hERG1 expression had a worse prognosis; (vi) the α -hERG1-MoAb could detect PDAC in vivo . Conclusions: hERG1 regulates PDAC malignancy and its expression, once validated in a larger cohort also comprising of late-stage, non-surgically resected cases, may be exploited for diagnostic and prognostic purposes in PDAC either ex vivo or in vivo .
机译：背景：hERG1通道在人类癌症中异常表达。缺乏hERG1通道在胰腺导管腺癌（PDAC）中的表达，功能作用和临床意义。方法：使用抗hERG1单克隆抗体（α-hERG1-MoAb），通过免疫组织化学在组装为组织微阵列的PDAC主要样品中检测hERG1的表达。在PDAC细胞系和原代培养中研究了hERG1的功能作用。在Pdx-1-Cre，LSL-Kras〜（G12D / +），LSL-Trp53〜（R175H / +）转基因（KPC）小鼠中研究了PDAC进展过程中ERG1的表达。使用Alexa-680标记的α-hERG1-MoAb通过光学成像确定体内ERG1的表达。结果：（i）59％的原发性PDAC中hERG1高水平表达; （ii）hERG1阻滞降低了PDAC细胞的生长和迁移; （iii）hERG1在物理上和功能上与表皮生长因子受体途径相关; （iv）在转基因小鼠中，ERG1在PanIN病变中表达，在PDAC中达到高表达水平; （v）原发性肿瘤显示高hERG1表达的PDAC患者预后较差; （vi）α-hERG1-MoAb可以在体内检测到PDAC。结论：hERG1调节PDAC恶性肿瘤，一旦在更大的队列中得到证实，其表达也包括晚期，非手术切除的病例，则hERG1可以在体内或体外用于PDAC的诊断和预后目的。

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