title: Intracellular calcium and breast-cancer cell-growth and differentiation.
abstract: The growth of normal human breast epithelial cells in vitro, as well as those of other cell types is strongly influenced by the concentration of calcium in the culture medium [Ca++]e. The aim of this study was to ascertain if calcium also affects breast tumor cell growth in vitro. To address this question, the metastatic breast cancer cells MCF-7 were grown at low (0.04 mM, L-Ca) and high (2.5 mM, H-Ca) [Ca++]e. In each culture condition, we estimated intracellular calcium levels (Ca++]i from Indo-1 fluorescence by the ratio method. We showed that [Ca++]i increased with [Ca++]e, the [Ca++]i values ranging from approximately 50 to 250 nM. Changes of [Ca++]i ware accompanied by changes of cell shape and cell kinetic parameters. In H-Ca, cells were flat and 3 times larger than in L-Ca and the percentage of cells in the S+G2+M phases as well as the percentage of Ki-67 positive cells rapidly dropped on days 3-4 of culture in contrast to cells grown in L-Ca. In H-Ca, the cell growth arrest corresponded to maximal [Ca++]i which was stable during the stationary phase; at that time, a switch from H-Ca to L-Ca resulted in a drop of [Ca++]i and a resumption of cell growth.. In H-Ca, modifications in cell differentiation parameters such as diminution of ER expression and increases of lipid content and EMA expression were observed as compared to cells grown m L-Ca. Our results suggest that MCF-7 cells have retained some calcium dependency and that agents that can increase [Ca++]i in breast tumor cells may limit their proliferation and trigger at least a partial differentiation.
authors.affiliation: UNIV LILLE FLANDRES ARTOIS,CTR ANAL IMAGES,F-59650 VILLENEUVE DASCQ,FRANCE. UNIV LILLE FLANDRES ARTOIS,BIOL DEV LAB,F-59650 VILLENEUVE DASCQ,FRANCE.
authors.forename: B
authors.initials: B
authors.lastname: Vandewalle
authors.forename: L
authors.initials: L
authors.lastname: Hornez
authors.forename: B
authors.initials: B
authors.lastname: Lassalle
authors.forename: F
authors.initials: F
authors.lastname: Revillion
authors.forename: M
authors.initials: M
authors.lastname: Bertout
authors.forename: J
authors.initials: J
authors.lastname: Lefebvre