Characterization of hERG1 channel role in mouse colorectal carcinogenesis

Antonella Fiore, Laura Carraresi, Angela Morabito, Simone Polvani, Angelo Fortunato, Elena Lastraioli, Angelo P. Femia, Emanuele De Lorenzo, Giovanna Caderni, Annarosa Arcangeli

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The human ether-à-go-go-related gene (hERG)1 K+ channel is upregulated in human colorectal cancer cells and primary samples. In this study, we examined the role of hERG1 in colorectal carcinogenesis using two mouse models: adenomatous polyposis coli (Apcmin/+) and azoxymethane (AOM)-treated mice. Colonic polyps of Apcmin/+ mice overexpressed mERG1 and their formation was reverted by the hERG1 blocker E4031. AOM was applied to either hERG1-transgenic (TG) mice, which overexpress hERG1 in the mucosa of the large intestine, or wild-type mice. A significant increase of both mucin-depleted foci and polyps in the colon of hERG1-TG mice was detected. Both the intestine of TG mice and colonic polyps of Apcmin/+ showed an upregulation of phospho-Protein Kinase B (pAkt)/vascular endothelial growth factor (VEGF-A) and an increased angiogenesis, which were reverted by treatment with E4031. On the whole, this article assigns a relevant role to hERG1 in the process of in vivo colorectal carcinogenesis.

Original languageEnglish (US)
Pages (from-to)583-594
Number of pages12
JournalCancer Medicine
Volume2
Issue number5
DOIs
StatePublished - Oct 2013

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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    Fiore, A., Carraresi, L., Morabito, A., Polvani, S., Fortunato, A., Lastraioli, E., Femia, A. P., De Lorenzo, E., Caderni, G., & Arcangeli, A. (2013). Characterization of hERG1 channel role in mouse colorectal carcinogenesis. Cancer Medicine, 2(5), 583-594. https://doi.org/10.1002/cam4.72