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Expression of Voltage-Gated Potassium Channels in Human and Mouse Colonic Carcinoma

Authors' Affiliations: ¹ Institut für Physiologie, Universität Regensburg, Regensburg, Germany and ² Institute for Pathology, University Hospital Basel, Basel, Switzerland

Requests for reprints: Karl Kunzelmann, Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, D-93053 Regensburg, Germany. Phone: 49-954-4302; Fax: 49-941-4315; E-mail: uqkkunze{at}mailbox.uq.edu.au.

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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