Indirect mechanism of oestradiol stimulation of cell proliferation of human breast cancer cell lines.

The human breast cancer cell line MCF-7 requires oestrogen to produce and promote growth of tumours in athymic mice. In vitro, however, MCF-7 cells proliferate rapidly without supply of oestrogen (Briand & Lykkesfeldt, 1984). Oestrogen stimulation of proliferation of MCF-7 cells can be achieved when the cells are grown at high concentration of newborn calf serum (NCS, 10%) or oestrogen deprived foetal calf serum (10%). The stimulation involves an abolishment of inhibitory activity present in the serum. The oestradiol stimulated cultures grow rapidly for a much longer time period and attain a much higher cell density than the unstimulated cultures. Oestrogen is specific for the promotion of cell proliferation and only oestrogen receptor positive cell lines with a functional oestrogen receptor mechanism can be stimulated. We assume that oestradiol acts directly on the cells and via the oestrogen receptor mechanism induces the synthesis of a substance which abolishes the inhibitory activity in serum. We call this mechanism of action an indirect stimulation of cell proliferation. A similar mechanism may exist in vivo since we find that serum from athymic mice contains a growth inhibitory activity towards MCF-7 cells and the inhibitory effect can be abolished by oestradiol.