title: Expression of voltage-gated potassium channels in human and mouse colonic carcinoma.
abstract: OBJECTIVE
  Voltage-gated Kv potassium channels, like ether a go-go (EAG) channels, have been recognized for their oncogenic potential in breast cancer and other malignant tumors.
  
  
  METHODS
  We examined the molecular and functional expression of Kv channels in human colonic cancers and colon of mice treated with the chemical carcinogens dimethylhydrazine and N-methyl-N-nitrosourea. The data were compared with results from control mice and animals with chemically induced DSS colitis.
  
  
  RESULTS
  Electrogenic salt transport by amiloride-sensitive Na+ channels and cyclic AMP-activated cystic fibrosis transmembrane conductance regulator Cl- channels were attenuated during tumor development and colitis, whereas Ca2+-dependent transport remained unchanged. Kv channels, in particular Eag-1, were enhanced during carcinogenesis. Multiplex reverse transcription-PCR showed increased mRNA expression for Kv1.3, Kv1.5, Kv3.1, and members of the Eag channel family, after dimethylhydrazine and N-methyl-N-nitrosourea treatment. Eag-1 protein was detected in the malignant mouse colon and human colonic cancers. Genomic amplification of Eag-1 was found in 3.4% of all human colorectal adenocarcinoma and was an independent marker of adverse prognosis.
  
  
  CONCLUSIONS
  The study predicts an oncogenic role of Kv and Eag channels for the development of colonic cancer. These channels may represent an important target for a novel pharmacotherapy of colonic cancer.
authors.affiliation: Institut für Physiologie, Universität Regensburg, Regensburg, Germany, and Institute for Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Jiraporn
authors.initials: J
authors.lastname: Ousingsawat
authors.forename: Melanie
authors.initials: M
authors.lastname: Spitzner
authors.forename: Supaporn
authors.initials: S
authors.lastname: Puntheeranurak
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.forename: Luigi
authors.initials: L
authors.lastname: Tornillo
authors.forename: Lukas
authors.initials: L
authors.lastname: Bubendorf
authors.forename: Karl
authors.initials: K
authors.lastname: Kunzelmann
authors.forename: Rainer
authors.initials: R
authors.lastname: Schreiber
mesh_terms: D000368:Aged; D000818:Animals; D001943:Breast Neoplasms; D003106:Colon / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D004238:Diverticulitis / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007249:Inflammation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024642:Potassium Channels, Voltage-Gated / Q000096:biosynthesis* / Q000737:chemistry
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; D024642:Potassium Channels, Voltage-Gated