Interleukin-1 Directly Regulates Hormone-Dependent Human Breast Cancer Cell Proliferationin Vitro

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Abstract
Direct in vitro effects of IL-1 on hormone-dependent (MCF-7 and ZR-75-B) and independent (HS-578-T and MDA-231) human breast cancer cell proliferation were investigated in short-term and long-term cell cultures. For short-term (48 h) studies [3H]thymidine uptake was used as an index of proliferation, while for long-term (12 day) cultures actual cell numbers were determined. Initial studies, conducted with MCF-7 cells, demonstrated that both forms of recombinant human IL-1 (.alpha. and .beta.) at 10-11 M inhibited [3H]thymindine uptake by MCF-7 by 70%, and by day 7 of the long-term study .alpha. and .beta. IL-1 at 10-11 M inhibited MCF-7 cell growth by 80%. IL-1, while inhibiting the growth of another hormone-dependent breast cancer cell line, ZR-75-B, had no effect on the hormone-independent cell lines MDA-231 and HS-578-T. The differing proliferative responses of the hormone-dependent and independent cells to IL-1 may, in part, be due to the expression of IL-1 receptors in these cells, in that MCF-7 cells express IL-1 receptors [dissociation constant (Kd) = 2.0 .times. 10-10 M; receptor density = 2,500 sites per cell and mol wt = 80,000] while the hormone-independent MDA-231 cells do not.