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Interleukin 1 Blocks Estradiol-stimulated Growth and Down-regulates the Estrogen Receptor in MCF-7 Breast Cancer Cells in Vitro¹

Surgery Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892

We studied the effect of interleukin 1 (IL-1) on estradiol stimulation of cell growth and estrogen receptor (ER) content in MCF-7 human breast cancer cells in vitro to determine if IL-1 altered cellular estradiol responsiveness. We found that IL-1 blocked estradiol-stimulated growth of these cells in a dose-dependent manner (complete antagonism at 1000 units/ml: day 7 mean growth = vehicle, 47.7 µg DNA; estradiol 10^-10 M, 95.1; IL-1/estradiol, 44.6) and at all concentrations of estradiol from 10^-8 to 10^-11 M. IL-1 in combination with trans-hydroxytamoxifen further inhibited estradiol-stimulated growth (vehicle = 44.8 µg DNA, estradiol = 108.3, estradiol/trans-hydroxytamoxifen = 47.8, IL-1/estradiol/trans-hydroxytamoxifen = 3.0, P < 0.01). Inhibition with trans-hydroxytamoxifen was IL-1 dose dependent (maximum = 97% at 1000 units/ml, P < 0.01) and estradiol dose dependent (reversible with 10^-8 M estradiol, maximum inhibition at 10^-10 M estradiol). Concomitantly, IL-1 down-regulated ER concentration by 38.0–43.7% (P < 0.01) as measured by immunoreactivity or Scatchard analysis, respectively. This occurred as early as 3 h without a change in the K_d (vehicle = 0.23 nM, IL-1 = 0.24 nM), persisted for at least 48 h, was dose dependent (maximum, 43.7% at 1000 units/ml, P < 0.01), and was blocked by cycloheximide. IL-1, however, did not block estradiol stimulation of progesterone receptor content (vehicle = 221.9, IL-1 = 238.9 fmol/mg protein) and did not block estradiol down-regulation of ER content. Furthermore, IL-1 alone did not alter levels of ER mRNA and did not alter estradiol down-regulation of ER mRNA. These findings indicate that while IL-1 antagonizes estradiol stimulation of growth and reduces ER content, its mechanism may involve other non-estrogen-regulated pathways.

¹ Presented at the 81st Annual Meeting of the American Association for Cancer Research, Washington, DC, May 25, 1990.

² To whom requests for reprints should be addressed, at Surgery Branch, National Cancer Institute, Bldg. 10, Rm 2B38, Bethesda, MD 20892.

Received 6/25/90. Accepted 12/20/90.

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