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.
2013
2
583
594
Goal 3: Good health and well-being for people
Antonella Fiore;Laura Carraresi;Angela Morabito;Simone Polvani;Angelo Fortunato;Elena Lastraioli;Angelo P. Femia;Emanuele De Lorenzo;Giovanna Caderni;Annarosa Arcangeli
File in questo prodotto:
File Dimensione Formato  
cancer medicine.pdf

Accesso chiuso

Tipologia: Versione finale referata (Postprint, Accepted manuscript)
Licenza: Open Access
Dimensione 3.02 MB
Formato Adobe PDF
3.02 MB Adobe PDF   Richiedi una copia

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/933354
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 19
  • ???jsp.display-item.citation.isi??? 17
social impact