The role of estrogens on the proliferation of human breast tumor cells (MCF-7)

Abstract

The cloned human breast tumor cell line C 7MCF7-173 behaved as an estrogen-dependent tumor in the nude mice. In contrast, E 2 added to serum-less media did not increase the multiplication rate of these cells over the values obtained in the control cultures. Media supplemented with charcoal-dextran stripped (CD) human female serum (FHS) resulted in inhibition of cell proliferation in a concentration-dependent pattern (40% = 20% > 10% > 5% > 2.5%). E 2 addition to all but the 2.5% CDFHS significantly increased the proliferation rate of these cells. The E 2 concentration required to attain maximal proliferation rate increased as the serum concentration of the medium increased (e.g. 3 × 10 −11M for 10% CDFHS, 3 × 10 −10M for 40% CDFHS). E 2 concentrations higher than the one needed to achieve maximal proliferation rate resulted in decreased cell yields (shut-off mechanism). Similar effects were obtained with synthetic and other natural estrogens. CD fetal bovine serum (FBS) also inhibited the proliferation of C 7MCF7-173 cells: however, at similar concentration the inhibitory effect of CDFHS was more potent than the one obtained with CDFBS. The addition of “growth factors” (insulin. Epidermal Growth Factor and transferrin) and non-estrogenic steroids to 10% CDFHS failed to overcome the inhibitory effect of this serum. These results suggest that: (1) human and fetal bovine sera contain a specific inhibitor of the proliferation of E 2-sensitive cells (estrocolyones), and (2) E 2 promotes cell proliferation by neutralizing this inhibitor.