The aryl hydrocarbon receptor (AHR)/AHR nuclear translocator (ARNT) heterodimer interacts with naturally occurring estrogen response elements

被引:100
作者
Klinge, CM [1 ]
Bowers, JL
Kulakosky, PC
Kamboj, KK
Swanson, HI
机构
[1] Univ Louisville, Sch Med, Dept Biochem & Mol Biol, Louisville, KY 40292 USA
[2] Univ Kentucky, Sch Med, Dept Pharmacol, Lexington, KY 40536 USA
关键词
estrogen receptor; aryl hydrocarbon receptor; xenobiotic response element; dioxin; estrogen response element;
D O I
10.1016/S0303-7207(99)00165-3
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
To determine the molecular mechanisms underlying the ''cross talk" between the activity of 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD), which binds to arylhydrocarbon receptor (AHR) and estradiol (E-2)-liganded estrogen receptor (ER), we first examined the initial step of estrogen action, ligand binding to ER. None of the AHR ligands tested, i.e. TCDD, benzo[a]pyrene, 3,3',4,4',5-pentachlorobiphenyl, beta-naphthoflavone, or alpha-naphthoflavone, bound to ER alpha. We report the first examination of TCDD interaction with ER beta:TCDD did not displace E-2 from ER beta. We then examined a second possible mechanism, i.e. direct inhibition of ER alpha binding to estrogen response elements (EREs) by the AHR/AHR nuclear translocator (ARNT) complex. The AHR/ARNT heterodimer did not bind either a full or half-site ERE. However, AHR/ARNT bound specifically to oligomers containing naturally occurring EREs derived from the human c-fos, pS2, and progesterone receptor (PR) gene promoters that include xenobiotic response element (XRE)-like sequences. In contrast, neither purified E-2-liganded-ER from calf uterus or recombinant human ER alpha bound a consensus XRE. TCDD inhibited E-2-activated reporter gene activity from a consensus ERE and from EREs in the pS2, PR, and Fos genes in transiently transfected MCF-7 human breast cancer cells. However, this inhibition was not reciprocal since E-2 did not inhibit TCDD-stimulated luciferase activity from the CYP1A1 promoter in transiently transfected MCF-7 or human endometrial carcinoma HEC-1A cells. We propose that at least part of the mechanism by which the AHR/ARNT complex inhibits estrogen action is by competitively inhibiting ERa binding to imperfect ERE sites, adjacent to or overlapping XREs. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:105 / 119
页数:15
相关论文
共 71 条
[1]   CHARACTERIZATION AND EPITOPE MAPPING OF A NEW PANEL OF MONOCLONAL-ANTIBODIES TO ESTRADIOL-RECEPTOR [J].
ABBONDANZA, C ;
DEFALCO, A ;
NIGRO, V ;
MEDICI, N ;
ARMETTA, I ;
MOLINARI, AM ;
MONCHARMONT, B ;
PUCA, GA .
STEROIDS, 1993, 58 (01) :4-12
[2]   COOPERATIVE BINDING OF ESTROGEN-RECEPTOR TO DNA DEPENDS ON SPACING OF BINDING-SITES, FLANKING SEQUENCE, AND LIGAND [J].
ANOLIK, JH ;
KLINGE, CM ;
HILF, R ;
BAMBARA, RA .
BIOCHEMISTRY, 1995, 34 (08) :2511-2520
[3]   Interaction of steroid hormone receptors with the transcription initiation complex [J].
Beato, M ;
SanchezPacheco, A .
ENDOCRINE REVIEWS, 1996, 17 (06) :587-609
[4]   NOVEL PROMOTER UPSTREAM OF THE HUMAN C-MYC GENE AND REGULATION OF C-MYC EXPRESSION IN B-CELL LYMPHOMAS [J].
BENTLEY, DL ;
GROUDINE, M .
MOLECULAR AND CELLULAR BIOLOGY, 1986, 6 (10) :3481-3489
[5]   ESTROGEN-RESPONSIVE ELEMENT OF THE HUMAN PS2 GENE IS AN IMPERFECTLY PALINDROMIC SEQUENCE [J].
BERRY, M ;
NUNEZ, AM ;
CHAMBON, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (04) :1218-1222
[6]   EFFECTS OF 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN (TCDD) ON CELL-GROWTH AND THE SECRETION OF THE ESTROGEN-INDUCED 34-KDA, 52-KDA AND 160-KDA PROTEINS IN HUMAN BREAST-CANCER CELLS [J].
BIEGEL, L ;
SAFE, S .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1990, 37 (05) :725-732
[7]   Use of toxic equivalency factors for risk assessment for dioxins and related compounds [J].
Birnbaum, LS ;
DeVito, MJ .
TOXICOLOGY, 1995, 105 (2-3) :391-401
[8]   ACTIVATION OF PS2 GENE-TRANSCRIPTION IS A PRIMARY RESPONSE TO ESTROGEN IN THE HUMAN-BREAST CANCER CELL-LINE MCF-7 [J].
BROWN, AMC ;
JELTSCH, JM ;
ROBERTS, M ;
CHAMBON, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (20) :6344-6348
[9]   Estrogen- and antiestrogen-responsiveness of HEC1A endometrial adenocarcinoma cells in culture [J].
Castro-Rivera, E ;
Safe, S .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1998, 64 (5-6) :287-295
[10]   POLYNUCLEAR AROMATIC HYDROCARBON CARCINOGENS AS ANTIESTROGENS IN MCF-7 HUMAN BREAST-CANCER CELLS - ROLE OF THE AH RECEPTOR [J].
CHALOUPKA, K ;
KRISHNAN, V ;
SAFE, S .
CARCINOGENESIS, 1992, 13 (12) :2233-2239