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.
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 humancolonic 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 mousecolon and humancolonic cancers. Genomic amplification of Eag-1 was found in 3.4% of all humancolorectal 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.
Authors: Violeta Zúñiga-García; María de Guadalupe Chávez-López; Valeria Quintanar-Jurado; Nayeli Belem Gabiño-López; Elisabeth Hernández-Gallegos; Juan Soriano-Rosas; Julio Isael Pérez-Carreón; Javier Camacho Journal: Dig Dis Sci Date: 2015-04-05 Impact factor: 3.199
Authors: María de Guadalupe Chávez-López; Julio Isael Pérez-Carreón; Violeta Zuñiga-García; José Díaz-Chávez; Luis A Herrera; Claudia Haydee Caro-Sánchez; Isabel Acuña-Macías; Patricio Gariglio; Elizabeth Hernández-Gallegos; Andrea Jazmín Chiliquinga; Javier Camacho Journal: Tumour Biol Date: 2015-03-18
Authors: Tinatin I Brelidze; Anne E Carlson; Douglas R Davies; Lance J Stewart; William N Zagotta Journal: PLoS One Date: 2010-09-02 Impact factor: 3.240