Two antiestrogens affect differently chromatin remodeling of trefoil factor 1 (pS2) gene and the fate of estrogen receptor in MCF7 cells.
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.
Giamarchi
Claire
C
Laboratoire de Biologie Moléculaire Eucaryote du CNRS, 118 route de Narbonne, F-31062 Toulouse cedex, France.
Chailleux
Catherine
C
Calligé
Mathide
M
Rochaix
Philippe
P
Trouche
Didier
D
Richard-Foy
Hélène
H
D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry / Q000235:genetics*; D003850:Deoxyribonuclease I / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D000077267:Fulvestrant; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D009376:Neoplasms, Hormone-Dependent; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D011960:Receptors, Estrogen / Q000032:analysis / Q000187:drug effects*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D000071163:Trefoil Factor-1; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D002843:Chromatin; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D011506:Proteins; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D013629:Tamoxifen; C016601:afimoxifene; D000077267:Fulvestrant; D004958:Estradiol; D003850:Deoxyribonuclease I