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

Ousingsawat, Jiraporn and Spitzner, Melanie and Puntheeranurak, Supaporn and Terracciano, Luigi and Tornillo, Luigi and Bubendorf, Lukas and Kunzelmann, Karl and Schreiber, Rainer (2007) Expression of voltage-gated potassium channels in human and mouse colonic carcinoma. CLINICAL CANCER RESEARCH, 13 (3). pp. 824-831. ISSN 1078-0432, 1557-3265

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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 Ca-21-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.

Item Type: Article
Uncontrolled Keywords: METHYL-N-NITROSOUREA; CELL-PROLIFERATION; ION CHANNELS; K+ CHANNELS; CANCER; CARCINOGENESIS; INDUCTION; MICE; MARKERS; ETHER;
Subjects: 500 Science > 570 Life sciences
Divisions: Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann
Depositing User: Dr. Gernot Deinzer
Date Deposited: 22 Dec 2020 10:11
Last Modified: 22 Dec 2020 10:11
URI: https://pred.uni-regensburg.de/id/eprint/33203

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