title: Characterization of hERG1 channel role in mouse colorectal carcinogenesis.
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.
authors.affiliation: Department of Experimental and Clinical Medicine, Section of Internal Medicine and Oncology, University of Florence, Florence, Italy; Istituto Toscano Tumori, Florence, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Fiore
authors.forename: Laura
authors.initials: L
authors.lastname: Carraresi
authors.forename: Angela
authors.initials: A
authors.lastname: Morabito
authors.forename: Simone
authors.initials: S
authors.lastname: Polvani
authors.forename: Angelo
authors.initials: A
authors.lastname: Fortunato
authors.forename: Elena
authors.initials: E
authors.lastname: Lastraioli
authors.forename: Angelo P
authors.initials: AP
authors.lastname: Femia
authors.forename: Emanuele
authors.initials: E
authors.lastname: De Lorenzo
authors.forename: Giovanna
authors.initials: G
authors.lastname: Caderni
authors.forename: Annarosa
authors.initials: A
authors.lastname: Arcangeli
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000098:blood supply / Q000378:metabolism; D000818:Animals; D001397:Azoxymethane; D063646:Carcinogenesis / Q000378:metabolism*; D002273:Carcinogens; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000139:chemically induced / Q000378:metabolism*; D004195:Disease Models, Animal; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007420:Intestine, Large / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D010880:Piperidines / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D011725:Pyridines / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D002273:Carcinogens; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C496884:KCNH1 protein, human; C000606913:KCNH2 protein, human; D009363:Neoplasm Proteins; D010880:Piperidines; D011725:Pyridines; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C063968:E 4031; D051057:Proto-Oncogene Proteins c-akt; D001397:Azoxymethane
keywords: Apcmin/+ mice; VEGF-A; azoxymethane; colorectal cancer; hERG1 channel