Differential activation of wild-type and variant forms of estrogen receptor α by synthetic and natural estrogenic compounds using a promoter containing three estrogen-responsive elements

Kyungsil Yoon, Lea Pallaroni, Matthew Stoner, Kevin Gaido, Stephen Safe

Research output: Contribution to journalArticle

Abstract

Structure-dependent estrogen receptor ± (ER±) agonist and antagonist activities of synthetic and natural estrogenic compounds were investigated in human HepG2, MDA-MB-231 and U2 cancer cell lines. Compounds used in this study include 4’-hydroxytamoxifen, ICI 182,780, bisphenol-A (BPA), 2’,4’,6’-trichloro-4-biphenylol (3Cl-PCB-OH), 2’,3’,4’,5’-tetrachloro-4-biphenylol (4Cl-PCB-OH), p-t-octylphenol, p-nonylphenol, naringenin, kepone, resveratrol, and 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE). Cells were transfected with a construct (pERE3) containing three tandem estrogen responsive elements (EREs) and either wild-type estrogen receptor ± (ER-wt) or variants expressing activation function-1 (ER-AF1) or AF-2 (ER-AF2). The ER agonist activities of the synthetic mono and dihydroxy aromatic compounds are comparable in all three-cell lines, whereas the activities of naringenin, kepone and resveratrol are dependent on cell context and expression of wild-type or variant forms of ER±. In contrast, the ER antagonist activities for these compounds were highly complex and, with the exception of 3Cl-PCB-OH, all compounds inhibited E2-induced wild-type or variant ER action. Results of this in vitro study suggest that the estrogenic and antiestrogenic activity of structurally diverse synthetic and natural estrogenic compounds is complex, and this is consistent with published data that often give contradictory results for these compounds.

Original languageEnglish (US)
Pages (from-to)25-32
Number of pages8
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume78
Issue number1
DOIs
StatePublished - 2001

Keywords

  • Activities
  • Differential
  • Estrogen receptor
  • Wild-type

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'Differential activation of wild-type and variant forms of estrogen receptor α by synthetic and natural estrogenic compounds using a promoter containing three estrogen-responsive elements'. Together they form a unique fingerprint.

Cite this