| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Endocrinology |
Department of Cell Biology, Baylor College of Medicine [Z. N.], and Department of Integrative Biology, Pharmacology, and Physiology, The University of Texas–Houston, Medical School [G. M. S., S. M. H.], Houston, Texas 77030
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 breast cancer. We now show for the first time that ICI 182,780 also exhibits potent antiprogestin activity at doses frequently used in laboratory investigations. The antiprogestin activity of ICI 182,780 was detected in HeLa, HepG2, and CV1 cells transiently transfected with either the A or B forms of the human progesterone receptor and a luciferase construct driven by a progesterone-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 M. The ICI compound produced 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 transfected androgen or glucocorticoid receptors. These results clearly establish that ICI 182,780 has significant antiprogestin activity in addition to its well-documented antiestrogenic activity and raises the possibility that both antihormonal properties of this compound are exhibited in laboratory studies and in the course of treatment of human breast tumors.
This article has been cited by other articles:
|
|
 |
|
  T. T. B. Vo and E.-B. Jeung An Evaluation of Estrogenic Activity of Parabens Using Uterine Calbindin-D9k Gene in an Immature Rat Model Toxicol. Sci., November 1, 2009; 112(1): 68 - 77. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Merlino, T. N. Welsh, H. Tan, L. J. Yi, V. Cannon, B. M. Mercer, and S. Mesiano Nuclear Progesterone Receptors in the Human Pregnancy Myometrium: Evidence that Parturition Involves Functional Progesterone Withdrawal Mediated by Increased Expression of Progesterone Receptor-A J. Clin. Endocrinol. Metab., May 1, 2007; 92(5): 1927 - 1933. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zhang, F. T F Tsai, and D. S Geller Differential interaction of RU486 with the progesterone and glucocorticoid receptors. J. Mol. Endocrinol., August 1, 2006; 37(1): 163 - 173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Bhattacharyya, A. V. Krishnan, S. Swami, and D. Feldman Fulvestrant (ICI 182,780) down-regulates androgen receptor expression and diminishes androgenic responses in LNCaP human prostate cancer cells. Mol. Cancer Ther., June 1, 2006; 5(6): 1539 - 1549. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Edovitsky, I. Lerner, E. Zcharia, T. Peretz, I. Vlodavsky, and M. Elkin Role of endothelial heparanase in delayed-type hypersensitivity Blood, May 1, 2006; 107(9): 3609 - 3616. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zhang, J. Simisky, F. T. F. Tsai, and D. S. Geller A critical role of helix 3-helix 5 interaction in steroid hormone receptor function PNAS, February 22, 2005; 102(8): 2707 - 2712. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wu, J. Richer, K. B. Horwitz, and S. M. Hyder Progestin-Dependent Induction of Vascular Endothelial Growth Factor in Human Breast Cancer Cells: Preferential Regulation by Progesterone Receptor B Cancer Res., March 15, 2004; 64(6): 2238 - 2244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Elkin, I. Cohen, E. Zcharia, A. Orgel, Z. Guatta-Rangini, T. Peretz, I. Vlodavsky, and H. K. Kleinman Regulation of Heparanase Gene Expression by Estrogen in Breast Cancer Cancer Res., December 15, 2003; 63(24): 8821 - 8826. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. R. Hubler, W. B. Denny, D. L. Valentine, J. Cheung-Flynn, D. F. Smith, and J. G. Scammell The FK506-Binding Immunophilin FKBP51 Is Transcriptionally Regulated by Progestin and Attenuates Progestin Responsiveness Endocrinology, June 1, 2003; 144(6): 2380 - 2387. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Wallace and J. A. Cidlowski Proteasome-mediated Glucocorticoid Receptor Degradation Restricts Transcriptional Signaling by Glucocorticoids J. Biol. Chem., November 9, 2001; 276(46): 42714 - 42721. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Lanari, I. Lüthy, C. A. Lamb, V. Fabris, E. Pagano, L. A. Helguero, N. Sanjuan, S. Merani, and A. A. Molinolo Five Novel Hormone-responsive Cell Lines Derived from Murine Mammary Ductal Carcinomas: In Vivo and in Vitro Effects of Estrogens and Progestins Cancer Res., January 1, 2001; 61(1): 293 - 302. [Abstract] [Full Text]
|
|
|
|
|
|
S. M. Hyder, Z. Nawaz, C. Chiappetta, and G. M. Stancel Identification of Functional Estrogen Response Elements in the Gene Coding for the Potent Angiogenic Factor Vascular Endothelial Growth Factor Cancer Res., June 1, 2000; 60(12): 3183 - 3190. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
