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

摘要: Structure-dependent estrogen receptor alpha (ER alpha) agonist and antagonist activities of synthetic natural estrogenic compounds were investigated in human HepG2, MDA-MB-231 U2 cancer cell lines. Compounds used 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, 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE). Cells transfected with a construct (pERE(3)) containing three tandem responsive elements (EREs) either wild-type (ER-wt) or variants expressing activation function-1 (ER-AF1) AF-2 (ER-AF2). The ER the mono dihydroxy aromatic are comparable all three-cell lines, whereas kepone resveratrol dependent on context expression variant forms alpha. In contrast, for these highly complex and, exception 3Cl-PCB-OH, inhibited E2-induced action. Results vitro suggest that antiestrogenic activity structurally diverse is complex, consistent published data often give contradictory results compounds.