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Expression of voltage-gated potassium channels in human and mouse colonic carcinoma.

Authors: Ousingsawat, J  Spitzner, M  Puntheeranurak, S  Terracciano, L  Tornillo, L  Bubendorf, L  Kunzelmann, K  Schreiber, R 
Citation: Ousingsawat J, etal., Clin Cancer Res. 2007 Feb 1;13(3):824-31.
Pubmed: (View Article at PubMed) PMID:17289873
DOI: Full-text: DOI:10.1158/1078-0432.CCR-06-1940

PURPOSE: 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. EXPERIMENTAL DESIGN: 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.


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RGD ID: 9693694
Created: 2015-02-11
Species: All species
Last Modified: 2015-02-11
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.