title: EGF stimulates Mg(2+) influx in mammary epithelial cells.
abstract: Magnesium is well established as a fundamental factor that regulates cell proliferation. However, the molecular mechanisms linking mitogenic signals, extracellular magnesium availability and intracellular effectors are still largely unknown. In the present study we sought to determine whether EGF regulates magnesium homeostasis in normal HC11 mammary epithelial cells. To this end, we measured Mg(2+) and Ca(2+) fluxes by confocal imaging in live cells loaded with specific fluorescent ion indicators (Mag-Fluo-4 and Fluo-4, respectively). EGF stimulation induces a rapid and sustained increase in intracellular Mg(2+), concomitantly with a rise in intracellular calcium. The increase in intracellular Mg(2+) derives from an influx from the extracellular compartment, and does not depend on Ca(2+). On the contrary, the increase in intracellular Ca(2+) derives from intracellular stores, and is impaired in the absence of extracellular magnesium. Inhibition of the EGF receptor tyrosine kinase by Tyrphostin AG1478 markedly inhibits EGF-induced Mg(2+) and Ca(2+) signals. These findings demonstrate that not only does Mg(2+) influx represent an important step in the physiological response of epithelial cells to EGF, but unexpectedly the EGF-induced Mg(2+) influx is essential for the Ca(2+) signal to occur.
authors.affiliation: Istituto di Patologia Generale, Facoltà di Medicina, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Trapani
authors.affiliation: Istituto di Patologia Generale, Facoltà di Medicina, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Arduini
authors.affiliation: Istituto di Patologia Generale, Facoltà di Medicina, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Luongo
authors.affiliation: Istituto di Patologia Generale, Facoltà di Medicina, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy. Electronic address: federica.wolf@rm.unicatt.it.
authors.forename: Federica I
authors.initials: FI
authors.lastname: Wolf
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D008274:Magnesium / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D008274:Magnesium
keywords: Ca(2+) signaling; Cell proliferation; MagT1; Mg(2+) transport; TRPM6; TRPM7