HERG1 gene expression as a specific tumor marker in colorectal tissues

Dolderer, J.; Schuldes, H.; Bockhorn, H.; Altmannsberger, M.; Lambers, C.; Zabern, D. von; Jonas, Dietger; Schwegler, Herbert; Linke, Rüdiger; Schröder, Ulrich H.

doi:10.1016/j.ejso.2009.05.009

Cited by 36 publications

(30 citation statements)

References 20 publications

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“…These results provide important clues for the potential pharmacological use of hERG modulators in cancer treatment. [18][19][20] ZC88 is a novel compound designed and synthesized by our institute based on a 4-aminopiperidine scaffold. Previous study showed that ZC88 exhibited a marked N-type calcium channel blockage.…”

Section: Discussionmentioning

confidence: 99%

ZC88, a novel 4-amino piperidine analog, inhibits the growth of neuroblastoma cells through blocking hERG potassium channel

Wei

Sun

Yan

et al. 2013

Cancer Biology & Therapy

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Section: Discussionmentioning

confidence: 99%

ZC88, a novel 4-amino piperidine analog, inhibits the growth of neuroblastoma cells through blocking hERG potassium channel

Wei

Sun

Yan

et al. 2013

Cancer Biology & Therapy

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“…More importantly, expression of hERG1 isoforms is elevated in primary human cancers, suggesting that this apparent upregulation is not due simply to altered gene expression with adaptation to in vitro culture conditions. Thus, hERG1 channels are overexpressed in endometrial adenocarcinoma (Cherubini et al, 2000), colorectal cancer (Lastraioli et al, 2004;Dolderer et al, 2010), gastric cancer (Shao et al, 2008), glioblastoma multiforme, myeloid leukemias , and acute lymphoblastic leukemias Smith et al, 2002); but expression is below detectable limits in noncancerous tissues. Interestingly, hERG1 expression in tumors correlates with metastatic cancers and a poorer prognosis (Lastraioli et al, 2004;Masi et al, 2005;Ding et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Long-Term Channel Block Is Required to Inhibit Cellular Transformation by Human Ether-à-Go-Go–Related Gene (hERG1) Potassium Channels

et al. 2014

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Both human ether-à-go-go-related gene (hERG1) and the closely related human ether-à-go-go (hEAG1) channel are aberrantly expressed in a large proportion of human cancers. In the present study, we demonstrate that transfection of hERG1 into mouse fibroblasts is sufficient to induce many features characteristic of malignant transformation. An important finding of this work is that this transformation could be reversed by chronic incubation (for 2-3 weeks) with the hERG channel blocker dofetilide (100 nM), whereas more acute applications (for 1-2 days) were ineffective. The hERG1 expression resulted in a profound loss of cell contact inhibition, multiple layers of overgrowing cells, and high saturation densities. Cells also changed from fibroblast-like to a more spindle-shaped morphology, which was associated with a smaller cell size, a dramatic increase in cell polarization, a reduction in the number of actin stress fibers, and less punctate labeling of focal adhesions. Analysis of single-cell migration and scratch-wound closure clearly demonstrated that hERG1-expressing cells migrated more rapidly than vector-transfected control cells. In contrast to previous studies on hEAG1, there were no increases in rates of proliferation, or loss of growth factor dependency; however, hERG1-expressing cells were capable of substrateindependent growth. Allogeneic transplantation of hERG1-expressing cells into nude mice resulted in an increased incidence of tumors. In contrast to hEAG1, the mechanism of cellular transformation is dependent on ion conduction. Trafficking-deficient and conduction-deficient hERG1 mutants also prevented cellular transformation. These results provide evidence that hERG1 expression is sufficient to induce cellular transformation by a mechanism distinct from hEAG1. The most important conclusion of this study is that selective hERG1 channel blockers have therapeutic potential in the treatment of hERG1-expressing cancers.

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“…The reason for the disparate Tl þ flux and APPC results is not clear; however, our results indicate that ciclopirox clearly modulates hERG channel activity. Since hERG channels are overexpressed in many tumor cells and modulation of hERG channel activity has resulted in inhibition of tumor growth, 44,45 it is tempting to speculate that the antitumor activity of ciclopirox is at least partially due to modulation of hERG channel activity.…”

Section: Resultsmentioning

confidence: 99%

Identification of HumanEther-à-go-goRelated Gene Modulators by Three Screening Platforms in an Academic Drug-Discovery Setting

Huang

Mangano

Hufeisen

et al. 2010

ASSAY and Drug Development Technologies

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The human Ether-à-go-go related gene (hERG) potassium channel is responsible for the rapid delayed rectifier potassium current that plays a critical role in the repolarization of cardiomyocytes during the cardiac action potential. In humans, inhibition of hERG by drugs can prolong the electrocardiographic QT interval, which, in rare instance, leads to ventricular arrhythmia and sudden cardiac death. As such, several medications that block hERG channels in vitro have been withdrawn from the market due to QT prolongation and arrhythmias. The current FDA guidelines recommend that drug candidates destined for human use be evaluated for potential hERG activity (www.fda.gov/downloads/Drugs/ GuidanceComplianceRegulatoryInformation/Guidances/ucm074963.pdf

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HERG1 gene expression as a specific tumor marker in colorectal tissues

Abstract: Introduction: Colorectal carcinomas exhibit a frequent recurrence after curative

Cited by 36 publications

References 20 publications

ZC88, a novel 4-amino piperidine analog, inhibits the growth of neuroblastoma cells through blocking hERG potassium channel

ZC88, a novel 4-amino piperidine analog, inhibits the growth of neuroblastoma cells through blocking hERG potassium channel

Long-Term Channel Block Is Required to Inhibit Cellular Transformation by Human Ether-à-Go-Go–Related Gene (hERG1) Potassium Channels

Identification of HumanEther-à-go-goRelated Gene Modulators by Three Screening Platforms in an Academic Drug-Discovery Setting

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