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Molecular Oncology Group (G.B.T., A.T., V.G.) Royal Victoria
Hospital Montréal, Québec, Canada H3A 1A1
Departments of Biochemistry, Medicine, and Oncology (V.G.)
McGill University Montréal, Québec, Canada
Mammalian Genetics Laboratory (N.G.C., D.J.G., N.A.J.)
ABL-Basic Research Program National Cancer Institute-Frederick
Cancer Research and Development Center Frederick, Maryland
21702
Laboratory of Molecular Endocrinology (F.L.) Centre
Hospitalier de l’Université Laval Research Center Ste-Foy,
Québec, Canada G1V 4G2
Estrogen receptor ß (ERß) is a novel steroid
receptor that is expressed in rat prostate and ovary. We have cloned
the mouse homolog of ERß and mapped the gene, designated
Estrb, to the central region of chromosome 12. The cDNA
encodes a protein of 485 amino acids that shares, respectively, 97%
and 60% identity with the DNA- and ligand-binding domains of mouse (m)
ER
. Mouse ERß binds to an inverted repeat spaced by three
nucleotides in a gel mobility shift assay and transactivates promoters
containing synthetic or natural estrogen response elements in an
estradiol (E2)-dependent manner. Scatchard
analysis indicates that mERß has slightly lower affinity for
E2 [dissociation constant
(Kd) = 0.5 nM] when
compared with mER (Kd = 0.2
nM). Antiestrogens, including
4-hydroxytamoxifen (OHT), ICI 182,780, and a novel compound, EM-800,
inhibit E2-dependent transactivation
efficiently. However, while OHT displays partial agonistic activity
with ER on a basal promoter linked to estrogen response elements in
Cos-1 cells, this effect is not observed with mERß. Cotransfection of
mERß and H-RasV12 causes enhanced activation
in the presence of E2. Mutagenesis of a serine
residue (position 60), located within a mitogen-activated protein
kinase consensus phosphorylation site abolishes the stimulatory effect
of Ras, suggesting that the activity of mERß is also regulated by the
mitogen-activated protein kinase pathway. Surprisingly, the coactivator
SRC-1 up-regulates mERß transactivation both in the absence and
presence of E2, and in vitro
interaction between SRC-1 and the ERß ligand-binding domain is
enhanced by E2. Moreover, the
ligand-independent stimulatory effect of SRC-1 on ERß transcriptional
activity is abolished by ICI 182,780, but not by OHT. Our results
demonstrate that while ERß shares many of the functional
characteristics of ER, the molecular mechanisms regulating the
transcriptional activity of mERß may be distinct from those of ER.
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 S. E. Aiyar, J.-l. Sun, A. L. Blair, C. A. Moskaluk, Y.-z. Lu, Q.-n. Ye, Y. Yamaguchi, A. Mukherjee, D.-m. Ren, H. Handa, et al. Attenuation of estrogen receptor {alpha}-mediated transcription through estrogen-stimulated recruitment of a negative elongation factor Genes & Dev., September 1, 2004; 18(17): 2134 - 2146. [Abstract] [Full Text] [PDF]
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 L. H. Smith, S. R. Coats, H. Qin, M. S. Petrie, J. W. Covington, M. Su, M. Eren, and D. E. Vaughan Differential and Opposing Regulation of PAI-1 Promoter Activity by Estrogen Receptor {alpha} and Estrogen Receptor {beta} in Endothelial Cells Circ. Res., August 6, 2004; 95(3): 269 - 275. [Abstract] [Full Text] [PDF]
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J. Laganiere, G. B. Tremblay, C. R. Dufour, S. Giroux, F. Rousseau, and V. Giguere A Polymorphic Autoregulatory Hormone Response Element in the Human Estrogen-related Receptor {alpha} (ERR{alpha}) Promoter Dictates Peroxisome Proliferator-activated Receptor {gamma} Coactivator-1{alpha} Control of ERR{alpha} Expression J. Biol. Chem., April 30, 2004; 279(18): 18504 - 18510. [Abstract] [Full Text] [PDF]
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F. Labrie, M. El-Alfy, L. Berger, C. Labrie, C. Martel, A. Belanger, B. Candas, and G. Pelletier The Combination of a Novel Selective Estrogen Receptor Modulator with an Estrogen Protects the Mammary Gland and Uterus in a Rodent Model: The Future of Postmenopausal Women's Health? Endocrinology, November 1, 2003; 144(11): 4700 - 4706. [Abstract] [Full Text] [PDF]
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P. Geraldes, M. G. Sirois, and J.-F. Tanguay Specific Contribution of Estrogen Receptors on Mitogen-Activated Protein Kinase Pathways and Vascular Cell Activation Circ. Res., September 5, 2003; 93(5): 399 - 405. [Abstract] [Full Text] [PDF]
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 T. S. A. Samy, R. Zheng, T. Matsutani, L. W. Rue III, K. I. Bland, and I. H. Chaudry Mechanism for normal splenic T lymphocyte functions in proestrus females after trauma: enhanced local synthesis of 17{beta}-estradiol Am J Physiol Cell Physiol, July 1, 2003; 285(1): C139 - C149. [Abstract] [Full Text] [PDF]
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B. Greco, L. S. Lubbers, and J. D. Blaustein Estrogen Receptor {beta} Messenger Ribonucleic Acid Expression in the Forebrain of Proestrous, Pregnant, and Lactating Female Rats Endocrinology, May 1, 2003; 144(5): 1869 - 1875. [Abstract] [Full Text] [PDF]
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Y. Bai and V. Giguere Isoform-Selective Interactions between Estrogen Receptors and Steroid Receptor Coactivators Promoted by Estradiol and ErbB-2 Signaling in Living Cells Mol. Endocrinol., April 1, 2003; 17(4): 589 - 599. [Abstract] [Full Text] [PDF]
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P. A. Orihuela, A. Parada-Bustamante, P. P. Cortes, C. Gatica, and H. B. Croxatto Estrogen Receptor, Cyclic Adenosine Monophosphate, and Protein Kinase A Are Involved in the Nongenomic Pathway by Which Estradiol Accelerates Oviductal Oocyte Transport in Cyclic Rats Biol Reprod, April 1, 2003; 68(4): 1225 - 1231. [Abstract] [Full Text] [PDF]
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 S. W. Cousins, M. E. Marin-Castano, D. G. Espinosa-Heidmann, A. Alexandridou, L. Striker, and S. Elliot Female Gender, Estrogen Loss, and Sub-RPE Deposit Formation in Aged Mice Invest. Ophthalmol. Vis. Sci., March 1, 2003; 44(3): 1221 - 1229. [Abstract] [Full Text] [PDF]
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Q. Lu, H. K. Surks, H. Ebling, W. E. Baur, D. Brown, D. C. Pallas, and R. H. Karas Regulation of Estrogen Receptor alpha -mediated Transcription by a Direct Interaction with Protein Phosphatase 2A J. Biol. Chem., February 7, 2003; 278(7): 4639 - 4645. [Abstract] [Full Text] [PDF]
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 M. Maira, C. Martens, E. Batsche, Y. Gauthier, and J. Drouin Dimer-Specific Potentiation of NGFI-B (Nur77) Transcriptional Activity by the Protein Kinase A Pathway and AF-1-Dependent Coactivator Recruitment Mol. Cell. Biol., February 1, 2003; 23(3): 763 - 776. [Abstract] [Full Text]
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M. E. Marin-Castano, S. J. Elliot, M. Potier, M. Karl, L. J. Striker, G. E. Striker, K. G. Csaky, and S. W. Cousins Regulation of Estrogen Receptors and MMP-2 Expression by Estrogens in Human Retinal Pigment Epithelium Invest. Ophthalmol. Vis. Sci., January 1, 2003; 44(1): 50 - 59. [Abstract] [Full Text] [PDF]
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 A. J. Jakimiuk, S. R. Weitsman, H.-W. Yen, M. Bogusiewicz, and D. A. Magoffin Estrogen Receptor {alpha} and {beta} Expression in Theca and Granulosa Cells from Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5532 - 5538. [Abstract] [Full Text] [PDF]
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D. A. Schreihofer, D. F. Rowe, E. F. Rissman, E. M. Scordalakes, J.-a. Gustafsson, and M. A. Shupnik Estrogen Receptor-{alpha} (ER{alpha}), But Not ER{beta}, Modulates Estrogen Stimulation of the ER{alpha}-Truncated Variant, TERP-1 Endocrinology, November 1, 2002; 143(11): 4196 - 4202. [Abstract] [Full Text] [PDF]
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