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Clin Cancer Res. 2007 Feb 1;13(3):824-31.

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

Author information

1
Institut für Physiologie, Universität Regensburg, Regensburg, Germany, and Institute for Pathology, University Hospital Basel, Basel, Switzerland.

Abstract

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.

PMID:
17289873
DOI:
10.1158/1078-0432.CCR-06-1940
[Indexed for MEDLINE]
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