Clinical cancer research : an official journal of the American Association for Cancer Research · 2007
Expression of voltage-gated potassium channels in human and mouse colonic carcinoma.
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Ousingsawat Jiraporn, Spitzner Melanie, Puntheeranurak Supaporn, Terracciano Luigi, Tornillo Luigi, Bubendorf Lukas, Kunzelmann Karl, Schreiber Rainer
Аннотация
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.
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.