title: Differential regulation of human Eag1 channel expression by serum and epidermal growth factor in lung and breast cancer cells.
abstract: Oncogenic ether à-go-go-1 (Eag1) potassium channels are overexpressed in most primary human solid tumors. Low oxygen and nutrient/growth factor concentrations play critical roles in tumorigenesis. However, the mechanisms by which tumor cells survive and proliferate under growth factor-depleted conditions remain elusive. Here, we investigated whether serum-deprived conditions and epidermal growth factor (EGF) regulate Eag1 expression in human lung and breast cancer cells. The human cancer cell lines A549 and MCF-7 (from the lungs and breast, respectively) were obtained from the American Type Culture Collection and cultured following the manufacturer's recommendations. Eag1 gene and protein expression were studied by real-time PCR and immunocytochemistry, respectively. Cell proliferation was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and ERK1/2 phosphorylation was investigated by Western blot. Serum-deprived conditions increased Eag1 mRNA and protein expression in both cell lines. This Eag1 upregulation was prevented by EGF and the ERK1/2 inhibitor U0126 in only lung cancer cells; vascular endothelial growth factor did not prevent Eag1 upregulation. Our results suggest that Eag1 may act as a survival and mitogenic factor under low-serum and nutrient conditions and may be a clinical target during the early stages of tumor development.
authors.affiliation: Department of Pharmacology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico.
authors.forename: Isabel
authors.initials: I
authors.lastname: Acuña-Macías
authors.affiliation: Department of Pharmacology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico.
authors.forename: Eunice
authors.initials: E
authors.lastname: Vera
authors.affiliation: Department of Pharmacology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico.
authors.forename: Alma Yolanda
authors.initials: AY
authors.lastname: Vázquez-Sánchez
authors.affiliation: Department of Physiology, Biophysics and Neurosciences, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico.
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Mendoza-Garrido
authors.affiliation: Department of Pharmacology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico.
authors.forename: Javier
authors.initials: J
authors.lastname: Camacho
keywords: EGF; ERK 1/2; epidermal growth factor; ether à-go-go; lung cancer; potassium channels; serum deprivation