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Ether à go-go Potassium Channels as Human Cervical Cancer Markers

¹ Pharmacology Section, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México City, México; ² Departamento de Biología de la Reproducción. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México; ³ Departamento de Ginecología, Hospital General "Dr. Manuel Gea González," México City, México; ⁴ Departamento de Biología, Facultad de Química. Universidad Nacional Autónoma de México, Ciudad Universitaria, México City, México; ⁵ Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas/Instituto Nacional de Cancerología, México City, México; and ⁶ Max-Planck-Institut für experimentelle Medizin, Abteilung Molekulare Biologie neuronaler Signale, Göttingen, Germany

Ether à go-go (EAG) potassium channels display oncogenic properties. In normal tissues, EAG mRNA is almost exclusively expressed in brain, but it is expressed in several somatic cancer cell lines, including HeLa, from cervix. Antisense experiments against eag reduce cell proliferation in some cancer cell lines, and inhibition of EAG-mediated currents has been suggested to decrease cell proliferation in a melanoma cell line. Because of the potential clinical relevance of EAG, we investigated EAG mRNA expression in the following fresh samples from human uterine cervix: 5 primary cultures obtained from cancerous biopsies, 1 cancerous fresh tissue, and 12 biopsies of control normal tissue. All of the control cervical samples came from patients with negative pap smears. Reverse transcription-PCR and Southern-blot experiments revealed eag expression in 100% of the cancerous samples and in 33% of the normal biopsies. Immunochemistry experiments showed the presence of EAG channel protein in cells from the primary cultures and in cervical cancer biopsies sections from the same patients. In addition, we looked for EAG-mediated currents in the cultures from cervical cancer cells. Here we show for the first time EAG channel activity in human tumors. Patch-clamp recordings showed typical EAG-mediated currents modulated by magnesium and displaying a pronounced Cole-Moore shift. Because EAG expression and channel activity have been suggested to be important in cell proliferation, our findings strongly support the idea of considering EAG as a tumor marker as well as a potential membrane therapeutic target for cervical cancer.

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