Nuclear thyroid hormone receptors in a human breast cancer cell line.

Proliferation of a human metastatic breast cancer cell line derived at the Michigan Cancer Foundation (MCF-7) was stimulated significantly (p < 0.05) by the addition of L-3,3 ,5-triiodothyronine (T3) to the culture medium. An optimal effect was observed near 5 x 10 I0 M. Thyroid hormone receptor was assayed by comparing the radioactive [125I]T3incorporated by MCF-7 cells incu bated in culture with and without unlabeled competitor. Bound [125I]T3in the nuclei was determined directly by counting Triton X-100-purified nuclear pellets. Saturable or competible binding was not demonstrable for whole cells. MCF-7 nuclei contain a relatively small number of spe cific T3-binding sites (20 fmol/100 ¿igDNA, or 1200 sites/ cell) with high affinity (K„ = 1 x 10 10 M). The relative effectiveness of unlabeled structural analogs to T3 as competitors for [125I]T3binding was: T3 = 3,5-diiodo-3'isopropyl-L-thyronine > o-3,3 ,5-triiodothyronîne > L-thyroxine = 3,3 ,5,5 -tetraiodo-L-thyroacetic acid > reverse 3,3',S'-triiodo-L-thyronine. The mono-and diiodotyrosines, bovine insulin, ovine prolactin, 17/3-estradiol, prostaglandin F,,,,,indomethacin, and propylthiouracil did not com pete for binding sites. Nuclear receptor levels were not altered by treatment of MCF-7 cells with these compounds or with T3 itself. Receptor levels also did not fluctuate with the growth phase. Our data establish the presence of receptors for thyroid hormone in nuclei of cells derived from a human breast cancer.