1. Two antiestrogens affect differently chromatin remodeling of trefoil factor 1 (pS2) gene and the fate of estrogen receptor in MCF7 cells
- Author
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Hélène Richard-Foy, Didier Trouche, Mathide Calligé, Philippe Rochaix, Catherine Chailleux, and Claire Giamarchi
- Subjects
Selective Estrogen Receptor Modulators ,Neoplasms, Hormone-Dependent ,Time Factors ,Blotting, Western ,Biophysics ,Estrogen receptor ,Biology ,Biochemistry ,Chromatin remodeling ,Structural Biology ,Tumor Cells, Cultured ,Genetics ,Deoxyribonuclease I ,Humans ,Promoter Regions, Genetic ,skin and connective tissue diseases ,MTA2 ,Fulvestrant ,Estrogen receptor beta ,Cell Nucleus ,Sp1 transcription factor ,Estradiol ,Tumor Suppressor Proteins ,Estrogen Antagonists ,Estrogen Receptor alpha ,Proteins ,Immunohistochemistry ,Chromatin ,Cell biology ,Tamoxifen ,Gene Expression Regulation ,Receptors, Estrogen ,Cancer research ,Trefoil Factor-1 ,Estrogen-related receptor gamma ,DNase I hypersensitive site ,Estrogen receptor alpha ,hormones, hormone substitutes, and hormone antagonists - Abstract
We show here that the two antagonists ICI 182 780, a pure estrogen antagonist, and 4-hydroxy-tamoxifen, a selective estrogen receptor modulator (SERM) have distinct effects on TFF1 (formerly pS2) gene chromatin structure and transcription. Indeed, ICI 182 780 decreased both the intensity of the hormone-dependent DNase I hypersensitive site pS2 HS-1 and transcription of the pS2 gene whereas 4-hydroxy-tamoxifen (OH-Tam) increased the intensity of pS2-HS1 and had no effect on pS2 gene transcription. Interestingly, these differential effects are associated with different fates of ERalpha following the two treatments: The ERalpha-OH-Tam complex was retained in the nucleus more efficiently than the ERalpha-estradiol complex. In contrast, ICI 182 780 provoked a rapid relocation of ERalpha complex to an insoluble nuclear fraction, followed by its degradation. Taken together, these data suggest that regulating the amount of ERalpha in the nucleus is a major way of action of estrogen antagonists with respect to chromatin remodeling and transcriptional control.
- Published
- 2002