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.
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. - In: CANCER MEDICINE. - ISSN 2045-7634. - ELETTRONICO. - 2:(2013), pp. 583-594. [10.1002/cam4.72]
Characterization of hERG1 channel role in mouse colorectal carcinogenesis
FIORE, ANTONELLA;CARRARESI, LAURA;POLVANI, SIMONE;LASTRAIOLI, ELENA;CADERNI, GIOVANNA;ARCANGELI, ANNAROSA
2013
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.File | Dimensione | Formato | |
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