The pure antiestrogen ICI 182,780 inhibits progestin-induced transcription

The pure antiestrogen ICI 182,780 binds to the estrogen receptor with high affinity and is currently in clinical trials for the treatment of human bre ast cancer. We now show for the first time that ICI 182,780 also exhibits p otent antiprogestin activity at doses frequently used in laboratory investi gations. The antiprogestin activity of ICI 182,780 aas detected in HeLa, He pG2, and CVI cells transiently transfected with either the A or B forms of the human progesterone receptor and a luciferase construct driven by a prog esterone-response element. ICI 182,780 inhibited progesterone-induced gene transcription in a dose-dependent fashion with maximum inhibition obtained at 10(-6) M and an IC50 of approximately 2 x 10(-7) at The ICI compound pro duced the same degree of inhibition as that obtained with the antiprogestin RU-486. The antiestrogen tamoxifen did not display antiprogestin activity in this test system, and ICI 182,780 did not inhibit the activity of transf ected androgen or glucocorticoid receptors. These results clearly establish that ICE 182,780 has significant antiprogestin activity in addition to its well-documented antiestrogenic activity and raises the possibility that bo th antihormonal properties of this compound are exhibited in laboratory stu dies and in the course of treatment of human breast tumors.