Open AccessCharacterization of hERG1 channel role in mouse colorectal carcinogenesis
Author(s) -
Fiore Antonella,
Carraresi Laura,
Morabito Angela,
Polvani Simone,
Fortunato Angelo,
Lastraioli Elena,
Femia Angelo P.,
Lorenzo Emanuele,
Caderni Giovanna,
Arcangeli Annarosa
Publication year - 2013
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.72
Subject(s) - azoxymethane , carcinogenesis , angiogenesis , downregulation and upregulation , cancer research , genetically modified mouse , colorectal cancer , vascular endothelial growth factor , transgene , medicine , chemistry , biology , cancer , vegf receptors , biochemistry , gene
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 (Apc min/+ ) and azoxymethane ( AOM )‐treated mice. Colonic polyps of Apc min/+ 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 Apc min/+ 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.